Ddavp Drug Information

The following clinically significant adverse reactions are described elsewhere in the labeling: Hyponatremia Hypotension and Hypertension Increased risk of thrombosis in patients with von Willebrand's Disease Type IIB Hypersensitivity reactions Fluid retention The following adverse reactions have been identified during post-approval use of DDAVP 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.

To report SUSPECTED ADVERSE REACTIONS, contact Ferring Pharmaceuticals Inc. at 1-888-FERRING (1-888-337-7464) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Other Drugs that may Increase Risk of Hyponatremia

The concomitant administration of DDAVP 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 DDAVP Injection concomitantly with these drugs and when doses of these drugs are increased.

Other Vasoconstrictors

DDAVP Injection can elevate blood pressure. Use of DDAVP Injection with other vasoconstrictors may require a reduction of the DDAVP Injection dosage.

Pregnancy Risk Summary Prolonged experience with DDAVP 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 received by a 60 kg patient based on body surface area). In an embryo-fetal development study and a pre- and postnatal development study in rabbits, desmopressin acetate was administered subcutaneously at doses of 2, 20 or 200 mcg/kg/day (embryo-fetal development) and 0.1, 1 or 10 mcg/kg/day (pre- and postnatal development) during the period of organogenesis (gestation days 6 to 18). No effects on maternal and fetal survival or morphology were observed in both studies at doses of up to 200 mcg/kg/day (215× the 18 mcg dose received by a 60 kg patient based on body surface area) nor were there effects in the pre- and postnatal development study on parturition, postnatal survival, growth, development or behavior, up to the highest dose tested of 10 mcg/kg/day (11 times the 18 mcg dose received by a 60 kg patient, based on body surface area).

Pediatric Use The safety and effectiveness of DDAVP have been established in pediatric patients 3 months of age and older with hemophilia A and von Willebrand's disease and pediatric patients aged 12 years and older with diabetes insipidus. The safety and effectiveness of DDAVP have not been established in infants less than 3 months of age with hemophilia A or von Willebrand's disease or pediatric patients under 12 years of age with diabetes insipidus. Use in infants and pediatric patients will require careful fluid intake restriction to prevent possible hyponatremia and water intoxication.

Fluid restriction should be discussed with the patient and/or guardian.

Injection is contraindicated in patients with known hypersensitivity to desmopressin acetate or to any of the components of DDAVP Injection. DDAVP 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. Hyponatremia or a history of hyponatremia, Use in Specific Populations ]. Known or suspected syndrome of inappropriate antidiuretic hormone (SIADH) secretion . Polydipsia . Concomitant use with loop diuretics.

Concomitant use with systemic or inhaled glucocorticoids . During illnesses that can cause fluid or electrolyte imbalance, such as gastroenteritis, salt-wasting nephropathies, or systemic infection . DDAVP 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 Moderate to severe renal impairment defined as a creatinine clearance below 50 mL/min Hyponatremia or a history of hyponatremia Known or suspected syndrome of inappropriate antidiuretic hormone (SIADH) secretion Polydipsia Concomitant use with loop diuretics or systemic or inhaled glucocorticoids During illnesses that can cause fluid or electrolyte imbalance Heart failure or uncontrolled hypertension

Overdosage of DDAVP 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. 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 DDAVP Injection 4 mcg/mL.