Desmopressin Acetate Prescribing Information
Desmopressin Acetate Injection can cause hyponatremia. Severe hyponatremia can be life-threatening if it is not promptly diagnosed and treated, leading to seizures, coma, respiratory arrest, or death
Desmopressin Acetate Injection is contraindicated in patients with hyponatremia (or a history of hyponatremia), with excessive fluid intake (e.g., polydipsia), using loop diuretics or systemic or inhaled glucocorticoids, with known or suspected SIADH, and/or illnesses that can cause fluid or electrolyte imbalances
Prior to starting or resuming Desmopressin Acetate Injection, ensure that the serum sodium concentration is normal. Limit fluid intake to a minimum from 1 hour before administration until 8 hours after administration. Use of Desmopressin Acetate Injection without concomitant reduction of fluid intake may lead to fluid retention and hyponatremia.
Monitor the serum sodium concentration within 1 week and approximately 1 month of initiating Desmopressin Acetate Injection, and periodically thereafter
Patients with conditions associated with fluid and electrolyte imbalance (i.e., cystic fibrosis, heart failure, and renal disorders), geriatric and pediatric patients, patients receiving concomitant treatments that also cause hyponatremia (i.e., tricyclic antidepressants, selective serotonin reuptake inhibitors, nonsteroidal anti-inflammatory drugs, chlorpromazine, opiate analgesics, carbamazepine, lamotrigine, thiazide diuretics and chlorpropamide), and patients with habitual or psychogenic polydipsia who may drink excessive amounts of water, may be at increased risk of hyponatremia
If hyponatremia occurs, Desmopressin Acetate Injection may need to be temporarily or permanently discontinued and treatment for the hyponatremia instituted, depending on the clinical circumstances, including the duration and severity of the hyponatremia.
Desmopressin Acetate Injection is contraindicated in patients with known hypersensitivity to desmopressin acetate or to any of the components of Desmopressin Acetate Injection
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
- 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
Desmopressin Acetate Injection can cause hyponatremia. Severe hyponatremia can be life-threatening if it is not promptly diagnosed and treated, leading to seizures, coma, respiratory arrest, or death
Desmopressin Acetate Injection is contraindicated in patients with hyponatremia (or a history of hyponatremia), with excessive fluid intake (e.g., polydipsia), using loop diuretics or systemic or inhaled glucocorticoids, with known or suspected SIADH, and/or illnesses that can cause fluid or electrolyte imbalances
Prior to starting or resuming Desmopressin Acetate Injection, ensure that the serum sodium concentration is normal. Limit fluid intake to a minimum from 1 hour before administration until 8 hours after administration. Use of Desmopressin Acetate Injection without concomitant reduction of fluid intake may lead to fluid retention and hyponatremia.
Monitor the serum sodium concentration within 1 week and approximately 1 month of initiating Desmopressin Acetate Injection, and periodically thereafter
Patients with conditions associated with fluid and electrolyte imbalance (i.e., cystic fibrosis, heart failure, and renal disorders), geriatric and pediatric patients, patients receiving concomitant treatments that also cause hyponatremia (i.e., tricyclic antidepressants, selective serotonin reuptake inhibitors, nonsteroidal anti-inflammatory drugs, chlorpromazine, opiate analgesics, carbamazepine, lamotrigine, thiazide diuretics and chlorpropamide), and patients with habitual or psychogenic polydipsia who may drink excessive amounts of water, may be at increased risk of hyponatremia
If hyponatremia occurs, Desmopressin Acetate Injection may need to be temporarily or permanently discontinued and treatment for the hyponatremia instituted, depending on the clinical circumstances, including the duration and severity of the hyponatremia.
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.
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 Injection in patients with factor VIII levels between 2% to 5%; however, these patients should be carefully monitored.
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.
Desmopressin Acetate Injection can cause hyponatremia. Severe hyponatremia can be life-threatening if it is not promptly diagnosed and treated, leading to seizures, coma, respiratory arrest, or death
Desmopressin Acetate Injection is contraindicated in patients with hyponatremia (or a history of hyponatremia), with excessive fluid intake (e.g., polydipsia), using loop diuretics or systemic or inhaled glucocorticoids, with known or suspected SIADH, and/or illnesses that can cause fluid or electrolyte imbalances
Prior to starting or resuming Desmopressin Acetate Injection, ensure that the serum sodium concentration is normal. Limit fluid intake to a minimum from 1 hour before administration until 8 hours after administration. Use of Desmopressin Acetate Injection without concomitant reduction of fluid intake may lead to fluid retention and hyponatremia.
Monitor the serum sodium concentration within 1 week and approximately 1 month of initiating Desmopressin Acetate Injection, and periodically thereafter
Patients with conditions associated with fluid and electrolyte imbalance (i.e., cystic fibrosis, heart failure, and renal disorders), geriatric and pediatric patients, patients receiving concomitant treatments that also cause hyponatremia (i.e., tricyclic antidepressants, selective serotonin reuptake inhibitors, nonsteroidal anti-inflammatory drugs, chlorpromazine, opiate analgesics, carbamazepine, lamotrigine, thiazide diuretics and chlorpropamide), and patients with habitual or psychogenic polydipsia who may drink excessive amounts of water, may be at increased risk of hyponatremia
If hyponatremia occurs, Desmopressin Acetate Injection may need to be temporarily or permanently discontinued and treatment for the hyponatremia instituted, depending on the clinical circumstances, including the duration and severity of the hyponatremia.
Desmopressin Acetate Injection can cause hyponatremia. Severe hyponatremia can be life-threatening if it is not promptly diagnosed and treated, leading to seizures, coma, respiratory arrest, or death
Desmopressin Acetate Injection is contraindicated in patients with hyponatremia (or a history of hyponatremia), with excessive fluid intake (e.g., polydipsia), using loop diuretics or systemic or inhaled glucocorticoids, with known or suspected SIADH, and/or illnesses that can cause fluid or electrolyte imbalances
Prior to starting or resuming Desmopressin Acetate Injection, ensure that the serum sodium concentration is normal. Limit fluid intake to a minimum from 1 hour before administration until 8 hours after administration. Use of Desmopressin Acetate Injection without concomitant reduction of fluid intake may lead to fluid retention and hyponatremia.
Monitor the serum sodium concentration within 1 week and approximately 1 month of initiating Desmopressin Acetate Injection, and periodically thereafter
Patients with conditions associated with fluid and electrolyte imbalance (i.e., cystic fibrosis, heart failure, and renal disorders), geriatric and pediatric patients, patients receiving concomitant treatments that also cause hyponatremia (i.e., tricyclic antidepressants, selective serotonin reuptake inhibitors, nonsteroidal anti-inflammatory drugs, chlorpromazine, opiate analgesics, carbamazepine, lamotrigine, thiazide diuretics and chlorpropamide), and patients with habitual or psychogenic polydipsia who may drink excessive amounts of water, may be at increased risk of hyponatremia
If hyponatremia occurs, Desmopressin Acetate Injection may need to be temporarily or permanently discontinued and treatment for the hyponatremia instituted, depending on the clinical circumstances, including the duration and severity of the hyponatremia.
Injection: Desmopressin Acetate Injection, USP, for intravenous or subcutaneous administration, is a clear, colorless sterile solution and is available as follows:
- 4 mcg per mL in a Single-Dose vial
- 40 mcg per 10 mL (4 mcg per mL) in a Multiple-Dose vial
Desmopressin Acetate Injection is contraindicated in patients with known hypersensitivity to desmopressin acetate or to any of the components of Desmopressin Acetate Injection
Hypersensitivity reactions including anaphylaxis have been reported with intravenous and intranasal desmopressin acetate, including cases of fatal anaphylaxis with intravenous desmopressin acetate. Desmopressin Acetate Injection is contraindicated in patients with known hypersensitivity to desmopressin acetate or to any of the components of Desmopressin Acetate Injection
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.
Desmopressin Acetate Injection, USP is a synthetic vasopressin analog for intravenous or subcutaneous use. It is chemically defined as follows:
1-(3-mercaptopropionic acid)-8-D-arginine vasopressin monoacetate (salt) trihydrate.
Mol. Wt. 1183.34
Molecular Formula: C46H64N14O12S2•C2H4O2•3H2O
Desmopressin Acetate Injection, USP is a clear, colorless sterile solution available in a 4 mcg per mL single-dose vial and a 40 mcg per 10 mL multiple-dose vial: Each mL contains 4 mcg of desmopressin acetate, USP which is equivalent to 3.6 mcg of desmopressin free base. The inactive ingredients in each mL are 9 mg sodium chloride (to adjust tonicity), 5 mg chlorobutanol, and q.s Water for Injection, USP. Hydrochloric acid is used to adjust pH to 3.5 to 5.
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,
8.5 Geriatric UseClinical studies of Desmopressin Acetate Injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
This drug is known to be substantially excreted by the kidney, and the risk of adverse 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. Desmopressin acetate is contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50 mL/min)
[see Contraindications (4), Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].Use of Desmopressin Acetate Injection in geriatric patients will require careful fluid intake restrictions to prevent possible hyponatremia and water intoxication. Fluid restriction should be discussed with the patient
[see Warnings and Precautions (5.1)].and8.6 Renal ImpairmentDesmopressin acetate is substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with renal impairment than patients with normal renal function. Desmopressin acetate is contraindicated in patients with estimated CLcr by Cockcroft-Gault equation less than 50 mL/min
[see Contraindications (4), Clinical Pharmacology (12.3)].].12.3 PharmacokineticsEliminationThe geometric mean terminal half-life is 2.8 hours.
MetabolismDesmopressin is not metabolized by human CYP450 system.
ExcretionAfter intravenous administration of 2 mcg, 52% of the dose was recovered in the urine within 24 hours as unchanged desmopressin.
Drug Interaction StudiesIn vitrostudies in human liver microsome preparations have shown that desmopressin does not inhibit the human CYP450 system. Noin vivointeraction studies have been performed with Desmopressin Acetate Injection.Specific PopulationsPatients with Renal ImpairmentA pharmacokinetic study was conducted in subjects with normal renal function and patients with mild, moderate, and severe renal impairment (n=24, 6 subjects each group) with a single 2 mcg dose of desmopressin acetate intravenous injection. The geometric mean terminal half-life was 2.8 hours in subjects with normal renal function, and 4, 6.6, and 8.7 hours in patients with mild, moderate, and severe renal impairment, respectively. In patients with mild, moderate and severe renal impairment, mean desmopressin area under the plasma drug concentration time curve (AUC) was 1.5 fold, 2.4 fold and 3.6 fold higher, respectively compared to that of subjects with normal renal function
. - Hyponatremia or a history of hyponatremia [see,
5.1 HyponatremiaDesmopressin Acetate Injection can cause hyponatremia. Severe hyponatremia can be life-threatening if it is not promptly diagnosed and treated, leading to seizures, coma, respiratory arrest, or death
[see Boxed Warning].Desmopressin Acetate Injection is contraindicated in patients with hyponatremia (or a history of hyponatremia), with excessive fluid intake (e.g., polydipsia), using loop diuretics or systemic or inhaled glucocorticoids, with known or suspected SIADH, and/or illnesses that can cause fluid or electrolyte imbalances
[see Contraindications (4), Drug Interactions (7)]. Avoid concomitant treatments that also cause hyponatremia.Prior to starting or resuming Desmopressin Acetate Injection, ensure that the serum sodium concentration is normal. Limit fluid intake to a minimum from 1 hour before administration until 8 hours after administration. Use of Desmopressin Acetate Injection without concomitant reduction of fluid intake may lead to fluid retention and hyponatremia.
Monitor the serum sodium concentration within 1 week and approximately 1 month of initiating Desmopressin Acetate Injection, and periodically thereafter
[see Dosage and Administration (2.1)]. Base the frequency of serum sodium monitoring on the patient’s risk of hyponatremia.Patients with conditions associated with fluid and electrolyte imbalance (i.e., cystic fibrosis, heart failure, and renal disorders), geriatric and pediatric patients, patients receiving concomitant treatments that also cause hyponatremia (i.e., tricyclic antidepressants, selective serotonin reuptake inhibitors, nonsteroidal anti-inflammatory drugs, chlorpromazine, opiate analgesics, carbamazepine, lamotrigine, thiazide diuretics and chlorpropamide), and patients with habitual or psychogenic polydipsia who may drink excessive amounts of water, may be at increased risk of hyponatremia
[see Contraindications (4)].If hyponatremia occurs, Desmopressin Acetate Injection may need to be temporarily or permanently discontinued and treatment for the hyponatremia instituted, depending on the clinical circumstances, including the duration and severity of the hyponatremia.
],7.1 Other Drugs that may Increase Risk of HyponatremiaThe 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 Pediatric UseThe safety and effectiveness of desmopressin acetate 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 desmopressin acetate 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
[see Warnings and Precautions (5.1)].].8.5 Geriatric UseClinical studies of Desmopressin Acetate Injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
This drug is known to be substantially excreted by the kidney, and the risk of adverse 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. Desmopressin acetate is contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50 mL/min)
[see Contraindications (4), Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].Use of Desmopressin Acetate Injection in geriatric patients will require careful fluid intake restrictions to prevent possible hyponatremia and water intoxication. Fluid restriction should be discussed with the patient
[see Warnings and Precautions (5.1)]. - Known or suspected syndrome of inappropriate antidiuretic hormone (SIADH) secretion [see.]
5.1 HyponatremiaDesmopressin Acetate Injection can cause hyponatremia. Severe hyponatremia can be life-threatening if it is not promptly diagnosed and treated, leading to seizures, coma, respiratory arrest, or death
[see Boxed Warning].Desmopressin Acetate Injection is contraindicated in patients with hyponatremia (or a history of hyponatremia), with excessive fluid intake (e.g., polydipsia), using loop diuretics or systemic or inhaled glucocorticoids, with known or suspected SIADH, and/or illnesses that can cause fluid or electrolyte imbalances
[see Contraindications (4), Drug Interactions (7)]. Avoid concomitant treatments that also cause hyponatremia.Prior to starting or resuming Desmopressin Acetate Injection, ensure that the serum sodium concentration is normal. Limit fluid intake to a minimum from 1 hour before administration until 8 hours after administration. Use of Desmopressin Acetate Injection without concomitant reduction of fluid intake may lead to fluid retention and hyponatremia.
Monitor the serum sodium concentration within 1 week and approximately 1 month of initiating Desmopressin Acetate Injection, and periodically thereafter
[see Dosage and Administration (2.1)]. Base the frequency of serum sodium monitoring on the patient’s risk of hyponatremia.Patients with conditions associated with fluid and electrolyte imbalance (i.e., cystic fibrosis, heart failure, and renal disorders), geriatric and pediatric patients, patients receiving concomitant treatments that also cause hyponatremia (i.e., tricyclic antidepressants, selective serotonin reuptake inhibitors, nonsteroidal anti-inflammatory drugs, chlorpromazine, opiate analgesics, carbamazepine, lamotrigine, thiazide diuretics and chlorpropamide), and patients with habitual or psychogenic polydipsia who may drink excessive amounts of water, may be at increased risk of hyponatremia
[see Contraindications (4)].If hyponatremia occurs, Desmopressin Acetate Injection may need to be temporarily or permanently discontinued and treatment for the hyponatremia instituted, depending on the clinical circumstances, including the duration and severity of the hyponatremia.
- Polydipsia [see.]
5.1 HyponatremiaDesmopressin Acetate Injection can cause hyponatremia. Severe hyponatremia can be life-threatening if it is not promptly diagnosed and treated, leading to seizures, coma, respiratory arrest, or death
[see Boxed Warning].Desmopressin Acetate Injection is contraindicated in patients with hyponatremia (or a history of hyponatremia), with excessive fluid intake (e.g., polydipsia), using loop diuretics or systemic or inhaled glucocorticoids, with known or suspected SIADH, and/or illnesses that can cause fluid or electrolyte imbalances
[see Contraindications (4), Drug Interactions (7)]. Avoid concomitant treatments that also cause hyponatremia.Prior to starting or resuming Desmopressin Acetate Injection, ensure that the serum sodium concentration is normal. Limit fluid intake to a minimum from 1 hour before administration until 8 hours after administration. Use of Desmopressin Acetate Injection without concomitant reduction of fluid intake may lead to fluid retention and hyponatremia.
Monitor the serum sodium concentration within 1 week and approximately 1 month of initiating Desmopressin Acetate Injection, and periodically thereafter
[see Dosage and Administration (2.1)]. Base the frequency of serum sodium monitoring on the patient’s risk of hyponatremia.Patients with conditions associated with fluid and electrolyte imbalance (i.e., cystic fibrosis, heart failure, and renal disorders), geriatric and pediatric patients, patients receiving concomitant treatments that also cause hyponatremia (i.e., tricyclic antidepressants, selective serotonin reuptake inhibitors, nonsteroidal anti-inflammatory drugs, chlorpromazine, opiate analgesics, carbamazepine, lamotrigine, thiazide diuretics and chlorpropamide), and patients with habitual or psychogenic polydipsia who may drink excessive amounts of water, may be at increased risk of hyponatremia
[see Contraindications (4)].If hyponatremia occurs, Desmopressin Acetate Injection may need to be temporarily or permanently discontinued and treatment for the hyponatremia instituted, depending on the clinical circumstances, including the duration and severity of the hyponatremia.
- Concomitant use with loop diuretics [see].
WARNING: HYPONATREMIADesmopressin Acetate Injection 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 Injection 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 Injection. 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 Injection may need to be temporarily or permanently discontinued[see Warnings and Precautions (5.1)].WARNING: HYPONATREMIASee full prescribing information for complete boxed warning.- Desmopressin Acetate Injection can cause hyponatremia, which may be life-threatening if severe. (5.1)
- Desmopressin Acetate Injection 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)
- Concomitant use with systemic or inhaled glucocorticoids [see.]
WARNING: HYPONATREMIADesmopressin Acetate Injection 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 Injection 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 Injection. 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 Injection may need to be temporarily or permanently discontinued[see Warnings and Precautions (5.1)].WARNING: HYPONATREMIASee full prescribing information for complete boxed warning.- Desmopressin Acetate Injection can cause hyponatremia, which may be life-threatening if severe. (5.1)
- Desmopressin Acetate Injection 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)
- During illnesses that can cause fluid or electrolyte imbalance, such as gastroenteritis, salt-wasting nephropathies, or systemic infection [see.]
WARNING: HYPONATREMIADesmopressin Acetate Injection 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 Injection 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 Injection. 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 Injection may need to be temporarily or permanently discontinued[see Warnings and Precautions (5.1)].WARNING: HYPONATREMIASee full prescribing information for complete boxed warning.- Desmopressin Acetate Injection can cause hyponatremia, which may be life-threatening if severe. (5.1)
- Desmopressin Acetate Injection 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)
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
The following clinically significant adverse reactions are described elsewhere in the labeling:
- Hyponatremia [see,
4 CONTRAINDICATIONSDesmopressin 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
- 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
]5.1 HyponatremiaDesmopressin Acetate Injection can cause hyponatremia. Severe hyponatremia can be life-threatening if it is not promptly diagnosed and treated, leading to seizures, coma, respiratory arrest, or death
[see Boxed Warning].Desmopressin Acetate Injection is contraindicated in patients with hyponatremia (or a history of hyponatremia), with excessive fluid intake (e.g., polydipsia), using loop diuretics or systemic or inhaled glucocorticoids, with known or suspected SIADH, and/or illnesses that can cause fluid or electrolyte imbalances
[see Contraindications (4), Drug Interactions (7)]. Avoid concomitant treatments that also cause hyponatremia.Prior to starting or resuming Desmopressin Acetate Injection, ensure that the serum sodium concentration is normal. Limit fluid intake to a minimum from 1 hour before administration until 8 hours after administration. Use of Desmopressin Acetate Injection without concomitant reduction of fluid intake may lead to fluid retention and hyponatremia.
Monitor the serum sodium concentration within 1 week and approximately 1 month of initiating Desmopressin Acetate Injection, and periodically thereafter
[see Dosage and Administration (2.1)]. Base the frequency of serum sodium monitoring on the patient’s risk of hyponatremia.Patients with conditions associated with fluid and electrolyte imbalance (i.e., cystic fibrosis, heart failure, and renal disorders), geriatric and pediatric patients, patients receiving concomitant treatments that also cause hyponatremia (i.e., tricyclic antidepressants, selective serotonin reuptake inhibitors, nonsteroidal anti-inflammatory drugs, chlorpromazine, opiate analgesics, carbamazepine, lamotrigine, thiazide diuretics and chlorpropamide), and patients with habitual or psychogenic polydipsia who may drink excessive amounts of water, may be at increased risk of hyponatremia
[see Contraindications (4)].If hyponatremia occurs, Desmopressin Acetate Injection may need to be temporarily or permanently discontinued and treatment for the hyponatremia instituted, depending on the clinical circumstances, including the duration and severity of the hyponatremia.
- Moderate to severe renal impairment defined as a creatinine clearance below 50 mL/min
- Hypotension and Hypertension [see]
5.2 Hypotension and HypertensionDesmopressin acetate may cause hypotension (with compensatory increase in heart rate) or hypertension. Monitor blood pressure during Desmopressin Acetate Injection administration, particularly in patients with a history of coronary artery insufficiency and/or hypertensive cardiovascular disease
[see Adverse Reactions (6), Drug Interactions (7.2)] - Increased risk of thrombosis in patients with von Willebrand’s Disease Type IIB [see]
5.3 Increased Risk of Thrombosis in Patients with von
Willebrand’s Disease Type IIBUse of desmopressin acetate in patients with Type IIB von Willebrand’s disease may result in platelet aggregation, thrombocytopenia, and possibly thrombosis.
- Hypersensitivity reactions [see]
5.4 Hypersensitivity ReactionsHypersensitivity reactions including anaphylaxis have been reported with intravenous and intranasal desmopressin acetate, including cases of fatal anaphylaxis with intravenous desmopressin acetate. Desmopressin Acetate Injection is contraindicated in patients with known hypersensitivity to desmopressin acetate or to any of the components of Desmopressin Acetate Injection
[see Contraindications (4)]. It is not known whether antibodies to Desmopressin Acetate Injection are produced after repeated injections. Monitor patients for signs or symptoms of hypersensitivity reactions during administration, interrupt treatment should a reaction occur, and manage medically. Permanently discontinue for serious hypersensitivity reaction[see Adverse Reactions (6)]. - Fluid retention [see]
5.5 Fluid RetentionDesmopressin acetate can cause fluid retention, which can worsen underlying conditions that are susceptible to volume status. Patients with heart failure or uncontrolled hypertension may be at increased risk. Desmopressin Acetate Injection is not recommended in patients at risk for increased intracranial pressure or those with a history of urinary retention. Advise patients to limit fluid intake
[see Patient Counseling Information (17)].
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
Desmopressin Acetate Injection, USP is a synthetic vasopressin analog for intravenous or subcutaneous use. It is chemically defined as follows:
1-(3-mercaptopropionic acid)-8-D-arginine vasopressin monoacetate (salt) trihydrate.
Mol. Wt. 1183.34
Molecular Formula: C46H64N14O12S2•C2H4O2•3H2O
Desmopressin Acetate Injection, USP is a clear, colorless sterile solution available in a 4 mcg per mL single-dose vial and a 40 mcg per 10 mL multiple-dose vial: Each mL contains 4 mcg of desmopressin acetate, USP which is equivalent to 3.6 mcg of desmopressin free base. The inactive ingredients in each mL are 9 mg sodium chloride (to adjust tonicity), 5 mg chlorobutanol, and q.s Water for Injection, USP. Hydrochloric acid is used to adjust pH to 3.5 to 5.
Desmopressin acetate increases plasma levels of factor VIII activity in patients with hemophilia and von Willebrand’s disease Type I.
The antidiuretic effects of desmopressin acetate are mediated by stimulation of vasopressin 2 (V2) receptors, thereby increasing water re-absorption in the kidney, and hence reducing urine production. Desmopressin acetate is a replacement hormone for antidiuretic hormone in the treatment of central diabetes insipidus. The change in structure of arginine vasopressin to desmopressin acetate resulted in increased duration of action and a decreased vasopressor action and decreased actions on visceral smooth muscle relative to the enhanced antidiuretic activity, so that clinically effective antidiuretic doses were usually below threshold levels for effects on vascular or visceral smooth muscle.