Desmopressin Acetate
FDA Drug Information • Also known as: Ddavp, Desmopressin Acetate
- Brand Names
- Ddavp, Desmopressin Acetate
- Route
- INTRAVENOUS, SUBCUTANEOUS
- Dosage Form
- INJECTION, SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
BOXED WARNING WARNING: HYPONATREMIA Desmopressin acetate can cause hyponatremia. Severe hyponatremia can be life-threatening, leading to seizures, coma, respiratory arrest, or death [see Warnings and Precautions (5.1)] . Desmopressin acetate is contraindicated in patients at increased risk of severe hyponatremia, such as patients with excessive fluid intake, illnesses that can cause fluid or electrolyte imbalances, and in those using loop diuretics or systemic or inhaled glucocorticoids [see Contraindications (4) and Warnings and Precautions (5.1)] . Ensure the serum sodium concentration is normal before starting or resuming desmopressin acetate. Measure serum sodium within 7 days and approximately 1 month after initiating therapy, and periodically during treatment. More frequently monitor serum sodium in patients 65 years of age and older and in patients at increased risk of hyponatremia [see Dosage and Administration (2.1) and Warnings and Precautions (5.1)] . If hyponatremia occurs, desmopressin acetate may need to be temporarily or permanently discontinued [see Warnings and Precautions (5.1)] . WARNING: HYPONATREMIA See full prescribing information for complete boxed warning. Desmopressin acetate can cause hyponatremia, which may be life threatening if severe. ( 5.1 ) Desmopressin acetate is contraindicated in patients at increased risk of severe hyponatremia, such as patients with excessive fluid intake, illnesses that can cause fluid or electrolyte imbalances, and in those using loop diuretics or systemic or inhaled glucocorticoids. ( 4 , 5.1 ) Ensure serum sodium concentration is normal before starting or resuming desmopressin acetate injection. Measure serum sodium within 1 week and approximately 1 month after starting therapy and periodically during treatment. More frequently monitor serum sodium in patients 65 years of age and older and in patients at increased risk of hyponatremia. ( 2.1 , 5.1 ) If hyponatremia occurs, interrupt or discontinue desmopressin acetate injection. ( 5.1 )
Description
11 DESCRIPTION Desmopressin acetate injection, USP is a synthetic vasopressin analog for intravenous or subcutaneous use. It is chemically defined as follows: Mol. Wt. 1183.34 Empirical Formula: C 46 H 64 N 14 O 12 S 2
What Is Desmopressin Acetate Used For?
1 INDICATIONS AND USAGE Desmopressin acetate injection is a vasopressin analog used for: Central Diabetes Insipidus - 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. ( 1.1 ) Hemophilia A- for patients with factor VIII coagulant activity levels greater than 5% to maintain hemostasis during surgical procedures and postoperatively or reduce bleeding with episodes of spontaneous or traumatic injuries such as hemarthroses, intramuscular hematomas, or mucosal bleeding. ( 1.2 ) von Willebrand’s disease (Type I) - for patients with mild to moderate disease with factor VIII levels greater than 5% to maintain hemostasis during surgical procedures or traumatic injuries such as hemarthroses, intramuscular hematomas, or mucosal bleeding. ( 1.3 ) Limitations of Use Desmopressin acetate is ineffective and not indicated for the treatment of nephrogenic diabetes insipidus. ( 1.3 ) von Willebrand’s disease (severe Type I) - not indicated for the treatment of patients with severe Type I von Willebrand’s disease and when there is evidence of an abnormal molecular form of factor VIII antigen. ( 1.3 ) 1.1 Central Diabetes Insipidus Desmopressin acetate injection 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. Limitations of Use: Desmopressin acetate is ineffective and not indicated for the treatment of nephrogenic diabetes insipidus. 1.2 Hemophilia A Desmopressin acetate injection is indicated for patients with hemophilia A with factor VIII coagulant activity levels greater than 5% without factor VIII antibodies to: Maintain hemostasis during surgical procedures and postoperatively Reduce bleeding with episodes of spontaneous or traumatic injuries such as hemarthroses, intramuscular hematomas, or mucosal bleeding. 1.3 von Willebrand’s Disease Desmopressin acetate injection is indicated for patients with mild to moderate von Willebrand’s disease (Type I) with factor VIII levels greater than 5% to: Maintain hemostasis during surgical procedures and postoperatively Reduce bleeding with episodes of spontaneous or traumatic injuries such as hemarthroses, intramuscular hematomas, or mucosal bleeding. Limitations of Use Desmopressin acetate is not indicated for the treatment of severe von Willebrand’s disease (Type I) and when there is evidence of an abnormal molecular form of factor VIII antigen [see Warnings and Precautions (5.2)].
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Diabetes Insipidus: The daily dose is 2 mcg to 4 mcg administered as one or two divided doses by subcutaneous or intravenous injection. The dosage must be determined for each patient and adjusted according to the pattern of response. ( 2.1 ) Hemophilia A and von Willebrand’s Disease (Type I): 0.3 mcg/kg (to a maximum of 20 mcg) administered by intravenous infusion. Dilute dose as appropriate. ( 2.1 ) See Full Prescribing Information for instructions on reconstitution, preparation, and administration ( 2 ). 2.1 Pretreatment Testing and On-Treatment Monitoring Diabetes Insipidus Prior to treatment with desmopressin acetate, assess serum sodium, urine volume and osmolality. Intermittently during treatment, assess serum sodium, urine volume and osmolality or plasma osmolality. Hemophilia A Prior to treatment with desmopressin acetate injection, verify that factor VIII coagulant activity levels are >5% and exclude the presence of factor VIII autoantibodies. Also assess serum sodium and aPTT prior to treatment. 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) Prior to treatment with desmopressin acetate injection, verify that factor VIII coagulant activity levels are >5% and exclude severe von Willebrand’s disease (Type I) and presence of abnormal molecular form of factor VIII antigen. During treatment with desmopressin acetate injection, assess serum sodium, bleeding time, factor VIII coagulant activity, ristocetin cofactor activity, and von Willebrand antigen to ensure that adequate levels are being achieved. For All Patients Receiving Repeated Doses: Restrict free water intake and monitor for hyponatremia. Ensure that serum sodium is normal prior to initiating or resuming treatment with desmopressin acetate injection. 2.2 Recommended Dosage Initiate fluid restriction during treatment with desmopressin acetate injection [see Warnings and Precautions (5.1), Use in Specific Populations (8.4, 8.5)]. Diabetes Insipidus: Treatment naïve patients: The recommended starting daily dosage is 2 mcg to 4 mcg administered as one or two divided doses by subcutaneous or intravenous injection. Do not dilute desmopressin acetate injection for the Diabetes Insipidus population. The morning and evening doses should be separately adjusted for an adequate diurnal rhythm of water turnover. Adjust dose based upon response to treatment estimated by two parameters: adequate duration of sleep and adequate, not excessive, water turnover. Patients changing from intranasal desmopressin: The recommended starting dose of desmopressin acetate injection is 1/10 th the daily maintenance intranasal dose administered by subcutaneous or intravenous injection as one or two divided doses Hemophilia A and von Willebrand’s Disease (Type I): The recommended dosage is 0.3 mcg/kg actual body...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hyponatremia [see Contraindications, Warnings and Precautions (5.1)] Hypotension and Hypertension [see Warnings and Precautions (5.2)] Increased risk of thrombosis in patients with von Willebrand’s Disease Type IIB [see Warnings and Precautions (5.3)] Hypersensitivity reactions [see Warnings and Precautions (5.4)] Fluid retention [see Warnings and Precautions (5.5)] The following adverse reactions have been identified during post-approval use of desmopressin acetate injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiovascular: Hypertension, hypotension, tachycardia, thrombotic events, fluid retention Digestive: Nausea, abdominal cramps Immune: Hypersensitivity reactions Integumentary: Erythema, swelling, burning pain, facial flushing Laboratory: Hyponatremia Nervous: Headache, hyponatremic seizures Common adverse reactions are abdominal cramps, burning pain, erythema, facial flushing, fluid retention, headache, hypersensitivity reactions, hypertension, hyponatremia, hyponatremic seizures, hypotension, nausea, swelling, tachycardia, and thrombotic events. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Gland Pharma Limited at 864-879-9994 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
Drug Interactions
7 DRUG INTERACTIONS Drugs that increase risk of hyponatremia: Require more frequent serum sodium monitoring. ( 7.1 ) Other vasoconstrictors: May require a reduction of the desmopressin acetate dosage. ( 7.2 ) 7.1 Other Drugs that may Increase Risk of Hyponatremia The concomitant administration of desmopressin acetate injection with other drugs that may increase the risk of water intoxication with hyponatremia, (e.g., tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine, opiate analgesics, thiazide diuretics, NSAIDs, lamotrigine, sulfonylureas, particularly chlorpropamide, oxybutynin and carbamazepine), requires more frequent serum sodium monitoring. Monitor serum sodium more frequently in patients taking desmopressin acetate injection concomitantly with these drugs and when doses of these drugs are increased [see Contraindications (4), Warnings and Precautions (5.1), Drug Interactions (7.1), Use in Specific Populations (8.4, 8.5)]. 7.2 Other Vasoconstrictors Desmopressin acetate injection can elevate blood pressure. Use of desmopressin acetate injection with other vasoconstrictors may require a reduction of the desmopressin acetate injection dosage [see Warnings and Precautions (5.2), Adverse Reactions (6)].
Contraindications
4 CONTRAINDICATIONS Desmopressin acetate injection is contraindicated in patients with known hypersensitivity to desmopressin acetate or to any of the components of desmopressin acetate injection [see Warnings and Precautions (5.4), Adverse Reactions (6), Description (11)]. Desmopressin acetate injection is contraindicated in patients with the following conditions due to an increased risk of hyponatremia: Moderate to severe renal impairment defined as a creatinine clearance below 50 mL/min [see Use in Specific Populations (8.5, 8.6) and Clinical Pharmacology (12.3)]. Hyponatremia or a history of hyponatremia [see Warnings and Precautions (5.1), Drug Interactions (7.1)], Use in Specific Populations (8.4, 8.5)]. Known or suspected syndrome of inappropriate antidiuretic hormone (SIADH) secretion [see Warnings and Precautions (5.1)] . Polydipsia [see Warnings and Precautions (5.1)] . Concomitant use with loop diuretics [see Boxed Warning]. Concomitant use with systemic or inhaled glucocorticoids [see Boxed Warning] . During illnesses that can cause fluid or electrolyte imbalance, such as gastroenteritis, salt-wasting nephropathies, or systemic infection [see Boxed Warning] . Desmopressin acetate injection is contraindicated in patients with the following conditions because fluid retention increases the risk of worsening the underlying condition: Heart failure Uncontrolled hypertension Known hypersensitivity to desmopressin acetate or to any of the components ( 4 ) Moderate to severe renal impairment defined as a creatinine clearance below 50 mL/min ( 4 ) Hyponatremia or a history of hyponatremia ( 4 ) Known or suspected syndrome of inappropriate antidiuretic hormone (SIADH) secretion ( 4 ) Polydipsia ( 4 ) Concomitant use with loop diuretics or systemic or inhaled glucocorticoids ( 4 ) During illnesses that can cause fluid or electrolyte imbalance ( 4 ) Heart failure or uncontrolled hypertension ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Prolonged experience with desmopressin acetate injection in pregnant women over several decades, based on the available published literature and case reports, have not identified a drug associated risk of major birth defects, miscarriage or other 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 reproductive and developmental studies following administration of desmopressin acetate during organogenesis to pregnant rats and rabbits, at doses 130- and 110- times, respectively, the recommended dose of 18 mcg for a 60 kg patient, based on body surface area (mg/m 2 ). The estimated background risk of major birth defects and miscarriage for the indicated population are unknown. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease Associated Maternal and Embryo-fetal Risk : Pregnant women with Hemophilia A or von Willebrand’s disease may be at an increased risk for bleeding diatheses and hemorrhagic events at delivery. An affected newborn may also be at risk of bleeding diatheses. Data Animal Data In a developmental toxicity study in rats, desmopressin acetate was administered intravenously at doses of 9.68, 48.4, or 241 mcg/kg/day during the period of organogenesis (gestations days 7 to 17). Laparohysterectomy for fetal examinations were conducted on gestation day 20 for twenty females in each group; the remaining 10 females were allowed to litter in order to determine any postnatal effects that might be attributable to pre-natal treatment. No effects were seen on maternal and fetal survival, growth and morphology or post-natal offspring survival, growth, development, behavior and reproductive performance up to 241 mcg/kg/day (130 times the 18 mcg dose...
Overdosage
10 OVERDOSAGE Overdosage of desmopressin acetate injection leads to prolonged duration of action with an increased risk of water retention and hyponatremia. Signs of overdose may include headaches, abdominal cramps, nausea, facial flushing, confusion, drowsiness, problems with passing urine and rapid weight gain due to fluid retention [see Warnings and Precautions (5.1)]. In case of overdosage, the dosage should be reduced, frequency of administration decreased, or the drug withdrawn according to the severity of the condition, serum sodium assessed, and hyponatremia treated appropriately. There is no known specific antidote for desmopressin acetate or desmopressin acetate injection, 4 mcg/mL.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Desmopressin acetate injection, USP is available as a sterile solution supplied in carton of ten 1 mL single-dose, type I glass vials with rubber stopper and aluminium seal, (NDC 68083-550-01) each containing 4 mcg desmopressin acetate, USP per mL. 16.2 Storage and Handling Store refrigerated 2° to 8°C (36° to 46°F).
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.