DESMOPRESSIN ACETATE- desmopressin acetate_injection

Desmopressin Acetate Injection USP Desmopressin Acetate has been shown to be more potent than arginine vasopressin in increasing plasma levels of factor VIII activity in patients with hemophilia and von Willebrand’s disease Type I. Dose-response studies were performed in healthy persons, using doses of 0.1 to 0.4 mcg/kg body weight, infused over a 10-minute period. Maximal dose response occurred at 0.3 to 0.4 mcg/kg. The response to Desmopressin Acetate of factor VIII activity and plasminogen activator is dose-related, with maximal plasma levels of 300 to 400 percent of initial concentrations obtained after infusion of 0.4 mcg/kg body weight. The increase is rapid and evident within 30 minutes, reaching a maximum at a point ranging from 90 minutes to two hours. The factor VIII related antigen and ristocetin cofactor activity were also increased to a smaller degree, but still are dose-dependent. The biphasic half-lives of Desmopressin Acetate were 7.8 and 75.5 minutes for the fast and slow phases, respectively, compared with 2.5 and 14.5 minutes for lysine vasopressin, another form of the hormone. As a result, Desmopressin Acetate provides a prompt onset of antidiuretic action with a long duration after each administration. The change in structure of arginine vasopressin to Desmopressin Acetate has resulted in a decreased vasopressor action and decreased actions on visceral smooth muscle relative to the enhanced antidiuretic activity, so that clinically effective antidiuretic doses are usually below threshold levels for effects on vascular or visceral smooth muscle. When administered by injection, Desmopressin Acetate has an antidiuretic effect about ten times that of an equivalent dose administered intranasally. The bioavailability of the subcutaneous route of administration was determined qualitatively using urine output data. The exact fraction of drug absorbed by that route of administration has not been quantitatively determined. The percentage increase of factor VIII levels in patients with mild hemophilia A and von Willebrand’s disease was not significantly different from that observed in normal healthy individuals when treated with 0.3 mcg/kg of Desmopressin Acetate infused over 10 minutes. Plasminogen activator activity increases rapidly after Desmopressin Acetate infusion, but there has been no clinically significant fibrinolysis in patients treated with Desmopressin Acetate. The effect of repeated Desmopressin Acetate administration when doses were given every 12 to 24 hours has generally shown a gradual diminution of the factor VIII activity increase noted with a single dose. The initial response is reproducible in any particular patient if there are 2 or 3 days between administrations. Human Pharmacokinetics CONTRAINDICATIONS

Hemophilia A Desmopressin Acetate Injection USP Desmopressin Acetate will often maintain hemostasis in patients with hemophilia A during surgical procedures and postoperatively when administered 30 minutes prior to scheduled procedure. Desmopressin Acetate 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 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 in patients with factor VIII levels between 2% to 5%; however, these patients should be carefully monitored. von Willebrand’s Disease (Type I) Desmopressin Acetate Injection USP Desmopressin Acetate will usually stop bleeding in mild to moderate von Willebrand’s patients with episodes of spontaneous or trauma-induced injuries such as hemarthroses, intramuscular hematomas or mucosal bleeding. Those von Willebrand’s disease patients who are least likely to respond are those with severe homozygous von Willebrand’s 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 to ensure that adequate levels are being achieved. Desmopressin Acetate is not indicated for the treatment of severe classic von Willebrand’s disease (Type I) and when there is evidence of an abnormal molecular form of factor VIII antigen. (See WARNINGS Diabetes Insipidus Desmopressin Acetate Injection USP Desmopressin Acetate 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 USP Desmopressin Acetate Injection USP The necessity for repeat administration of Desmopressin Acetate 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 Diabetes Insipidus Desmopressin Acetate Injection USP 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 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 Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Geriatric Use CLINICAL PHARMACOLOGY CONTRAINDICATIONS PRECAUTIONS

Infrequently, Desmopressin Acetate has produced transient headache, nausea, mild abdominal cramps and vulval pain. These symptoms disappeared with reduction in dosage. Occasionally, injection of Desmopressin Acetate has produced local erythema, swelling or burning pain. Occasional facial flushing has been reported with the administration of Desmopressin Acetate. Desmopressin Acetate Injection USP Desmopressin Acetate Injection USP See WARNINGS Post Marketing Desmopressin Acetate Injection USP

Desmopressin Acetate Injection USP Desmopressin Acetate Injection USP Desmopressin Acetate is contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50 mL/min). Desmopressin Acetate is contraindicated in patients with hyponatremia or a history of hyponatremia.

WARNINGS
Very rare cases of hyponatremia have been reported from world-wide postmarketing experience in patients treated with Desmopressin Acetate (desmopressin acetate). Desmopressin Acetate is a potent antidiuretic which, when administered, may lead to water intoxication and/or hyponatremia. Unless properly diagnosed and treated hyponatremia can be fatal. Therefore, fluid restriction is recommended and should be discussed with the patient and/or guardian. Careful medical supervision is required. When Desmopressin Acetate Injection is administered to patients who do not have need of antidiuretic hormone for its antidiuretic effect, in particular in pediatric and geriatric patients, fluid intake should be adjusted downward to decrease the potential occurrence of water intoxication and hyponatremia. (See PRECAUTIONS Desmopressin Acetate should not be used to treat patients with Type IIB von Willebrand’s disease since platelet aggregation may be induced. Desmopressin Acetate should be used with caution in patients with habitual or psychogenic polydipsia who may be more likely to drink excessive amounts of water, putting them at greater risk of hyponatremia.
OVERDOSAGE
Signs of overdose may include confusion, drowsiness, continuing headache, problems with passing urine and rapid weight gain due to fluid retention. (See WARNINGS There is no known specific antidote for desmopressin acetate or Desmopressin Acetate Injection USP An oral LD 50

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