DESMOPRESSIN: 3,903 Adverse Event Reports & Safety Profile

Desmopressin Acetate Injection USP (desmopressin acetate) is a synthetic vasopressin analog for intravenous or subcutaneous use. It is chemically defined as follows: Mol. Wt.

1129.27 Empirical Formula: C 46 H 64 N 14 O 12 S 2

• C 2 H 4 O 2 1-(3-mercaptopropionic acid)-8-D-arginine vasopressin monoacetate (salt)

Desmopressin

Acetate solution for injection is a sterile solution in a 1 mL single-dose vial: Each mL contains 4 mcg of desmopressin acetate which is equivalent to 3.6 mcg of desmopressin free base. The inactive ingredients are sodium chloride, chlorobutanol (5 mg per mL), hydrochloric acid and water for injection. Sodium chloride is used to adjust tonicity. Hydrochloric acid is used to adjust pH.

Desmopressin

Acetate solution for injection is a sterile solution in a 10 mL multiple-dose vial: Each mL contains 4 mcg of desmopressin acetate which is equivalent to 3.6 mcg of desmopressin free base. The inactive ingredients are sodium chloride, chlorobutanol (5 mg per mL), hydrochloric acid and water for injection. Sodium chloride is used to adjust tonicity. Hydrochloric acid is used to adjust pH. desmopressin-structure

INDICATIONS AND USAGE 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.

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, USP, 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, USP, 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, USP, 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, USP.

2.2 Recommended Dosage Initiate fluid restriction during treatment with Desmopressin Acetate Injection, USP <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.4 , 8.5 )]</span>.

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, USP 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, USP 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 weight (to a maximum of 20 mcg) administered by intravenous infusion over 15 minutes to 30 minutes. If used preoperatively, administer 30 minutes prior to the procedure. If used to reduce spontaneous or traumatic bleeding, doses may be repeated after 8 hours to 12 hours and once daily thereafter, if needed, based upon clinical condition and von Willebrand factor and factor VIII levels. 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. Tachyphylaxis (lessening of response) with repeated administration (i.e., given more frequently than every 48 hours) may occur. The initial response is reproducible if Desmopressin Acetate is administered every 2 to 3 days.

2.3 Preparation and Administration for Patients with Hemophilia A and von Willebrand&apos;s Disease (Type I) Prepare the solution for infusion using aseptic technique. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Withdraw the necessary volume of Desmopressin Acetate Injection, USP from the vial and dilute by adding to the infusion bag of 0.9% Sodium Chloride Injection, USP per Table 1 .

Dilute Desmopressin Acetate

Injection, USP in sterile 0.9% Sodium Chloride Injection, USP and infuse slowly over 15 minutes to 30 minutes. The volume of diluent is weight-based.

See Table

1 for volume of diluent to use.

Table

1: Volume of Diluent Required Patient Weight Volume of 0.9% Sodium Chloride Injection, USP for dilution 10 kg or less 10 mL More than 10 kg 50 mL Monitor blood pressure and pulse during infusion.

2.4 Switching Between Desmopressin Acetate Formulations Desmopressin Acetate is also available as nasal spray and tablet dosage forms. When switching between formulations, the below text is meant as guidance for starting dose. However, dose should always be titrated individually according to the diuresis (antidiuretic response) and electrolyte status (serum sodium) of the patient. When switching from Desmopressin Acetate Nasal Spray to Desmopressin Acetate Injection, USP, the starting dose is one-tenth times the Desmopressin Acetate Nasal Spray dose. When switching from Desmopressin Acetate Tablets to Desmopressin Acetate Injection, USP, titrate dose individually according to the diuresis (antidiuretic response) and electrolyte status (serum sodium) due to the large variability in both PK and PD. Monitor patients closely during the initial dose titration period.

Desmopressin Acetate Injection USP is contraindicated in patients with known hypersensitivity to desmopressin acetate or to any of the components of Desmopressin Acetate Injection USP [see Warnings and Precautions (5.4) , Adverse Reactions (6) , Description (11) ] .

Desmopressin Acetate

Injection USP 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 USP 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 )

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 Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

AND PRECAUTIONS Hypotension and Hypertension: May cause hypotension with compensatory increase in heart rate or hypertension. Monitor blood pressure during Desmopressin Acetate Injection administration, especially in patients with heart disease. ( 5.2 )

Increased

Risk of Thrombosis in Patients with von Willebrand’s Disease Type IIB: Use of Desmopressin Acetate Injection in patients with Type IIB von Willebrand’s disease may cause thrombosis due to platelet aggregation. ( 5.3 )

Hypersensitivity

Reactions: Severe reactions have occurred. Monitor for reactions during administration and interrupt if reaction occurs. ( 5.4 )

Fluid

Retention: Fluid retention can worsen underlying conditions that are susceptible to volume status. Not recommended in patients at risk for increased intracranial pressure or with a history of urinary retention. ( 5.5 )

5.1 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 <span class="opacity-50 text-xs">[see Boxed Warning ]</span>.

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.

5.2 Hypotension and Hypertension Desmopressin Acetate Injection 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 <span class="opacity-50 text-xs">[see Adverse Reactions ( 6 ), Drug Interactions ( 7.2 )]</span>

5.3 Increased Risk of Thrombosis in Patients with von Willebrand&apos;s Disease Type IIB Use of Desmopressin Acetate Injection in patients with Type IIB von Willebrand’s disease may result in platelet aggregation, thrombocytopenia, and possibly thrombosis.

5.4 Hypersensitivity Reactions Hypersensitivity reactions including anaphylaxis have been reported with intravenous and intranasal Desmopressin Acetate Injection, including cases of fatal anaphylaxis with intravenous Desmopressin Acetate Injection.

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 )].

5.5 Fluid Retention Desmopressin Acetate Injection 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 )].

PRECAUTIONS General: For injection use only.

Desmopressin Acetate

Injection (desmopressin acetate) 4 mcg/mL has infrequently produced changes in blood pressure causing either a slight elevation in blood pressure or a transient fall in blood pressure and a compensatory increase in heart rate. The drug should be used with caution in patients with coronary artery insufficiency and/or hypertensive cardiovascular disease.

Desmopressin Acetate

Injection (desmopressin acetate) should be used with caution in patients with conditions associated with fluid and electrolyte imbalance, such as cystic fibrosis, heart failure and renal disorders, because these patients are prone to hyponatremia. There have been rare reports of thrombotic events following Desmopressin Acetate Injection 4 mcg/mL in patients predisposed to thrombus formation. No causality has been determined, however, the drug should be used with caution in these patients. Severe allergic reactions have been reported rarely. Anaphylaxis has been reported rarely with intravenous and intranasal Desmopressin Acetate Injection, including isolated cases of fatal anaphylaxis with intravenous Desmopressin Acetate Injection. It is not known whether antibodies to Desmopressin Acetate Injection 4 mcg/mL are produced after repeated injections. Hemophilia A: Laboratory tests for assessing patient status include levels of factor VIII coagulant, factor VIII antigen and factor VIII ristocetin cofactor (von Willebrand factor) as well as activated partial thromboplastin time. Factor VIII coagulant activity should be determined before giving Desmopressin Acetate Injection for hemostasis. If factor VIII coagulant activity is present at less than 5% of normal, Desmopressin Acetate Injection should not be relied on. von Willebrand’s Disease: Laboratory tests for assessing patient status include levels of factor VIII coagulant activity, factor VIII ristocetin cofactor activity, and factor VIII von Willebrand factor antigen. The skin bleeding time may be helpful in following these patients.

Diabetes

Insipidus: Laboratory tests for monitoring the patient include urine volume and osmolality. In some cases, plasma osmolality may be required.

Drug

Interactions: Although the pressor activity of Desmopressin Acetate Injection is very low compared with the antidiuretic activity, use of doses as large as 0.3 mcg/kg of Desmopressin Acetate Injection with other pressor agents should be done only with careful patient monitoring. The concomitant administration of drugs that may increase the risk of water intoxication with hyponatremia, (e.g., tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine, opiate analgesics, NSAIDs, lamotrigine and carbamazepine) should be performed with caution.

Desmopressin Acetate

Injection has been used with epsilon aminocaproic acid without adverse effects. Carcinogenesis, Mutagenesis, Impairment of Fertility: Studies with Desmopressin Acetate Injection have not been performed to evaluate carcinogenic potential, mutagenic potential or effects on fertility. Pregnancy: Fertility studies have not been done. Teratology studies in rats and rabbits at doses from 0.05 to 10 mcg/kg/day (approximately 0.1 times the maximum systemic human exposure in rats and up to 38 times the maximum systemic human exposure in rabbits based on surface area, mg/m 2 ) revealed no harm to the fetus due to Desmopressin Acetate Injection. There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Several publications of desmopressin acetate’s use in the management of diabetes insipidus during pregnancy are available; these include a few anecdotal reports of congenital anomalies and low birth weight babies. However, no causal connection between these events and desmo- pressin acetate has been established. A fifteen year, Swedish epidemiologic study of the use of desmopressin acetate in pregnant women with diabetes insipidus found the rate of birth defects to be no greater than that in the general population; however, the statistical power of this study is low. As opposed to preparations containing natural hormones, desmopressin acetate in antidiuretic doses has no uterotonic action and the physician will have to weigh the therapeutic advantages against the possible risks in each case.

Nursing

Mothers: There have been no controlled studies in nursing mothers. A single study in postpartum women demonstrated a marked change in plasma, but little if any change in assayable Desmopressin Acetate Injection in breast milk following an intranasal dose of 10 mcg. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Desmopressin Acetate Injection is admin- istered to a nursing woman.

Pediatric

Use: 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 .)

Desmopressin Acetate Injection

4 mcg/mL should not be used in infants less than three months of age in the treatment of hemophilia A or von Willebrand’s disease; safety and effectiveness in pediatric patients under 12 years of age with diabetes insipidus have not been established.

Geriatric

Use: Clinical 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 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.

Desmopressin Acetate

Injection is contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50 mL/min). (See CLINICAL PHARMACOLOGY , Human Pharmacokinetics and CONTRAINDICATIONS .) 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 .)

General: For injection use only.

Desmopressin Acetate

Injection (desmopressin acetate) 4 mcg/mL has infrequently produced changes in blood pressure causing either a slight elevation in blood pressure or a transient fall in blood pressure and a compensatory increase in heart rate. The drug should be used with caution in patients with coronary artery insufficiency and/or hypertensive cardiovascular disease.

Desmopressin Acetate

Injection (desmopressin acetate) should be used with caution in patients with conditions associated with fluid and electrolyte imbalance, such as cystic fibrosis, heart failure and renal disorders, because these patients are prone to hyponatremia. There have been rare reports of thrombotic events following Desmopressin Acetate Injection 4 mcg/mL in patients predisposed to thrombus formation. No causality has been determined, however, the drug should be used with caution in these patients. Severe allergic reactions have been reported rarely. Anaphylaxis has been reported rarely with intravenous and intranasal Desmopressin Acetate Injection, including isolated cases of fatal anaphylaxis with intravenous Desmopressin Acetate Injection. It is not known whether antibodies to Desmopressin Acetate Injection 4 mcg/mL are produced after repeated injections.

Hemophilia A: Laboratory tests for assessing patient status include levels of factor VIII coagulant, factor VIII antigen and factor VIII ristocetin cofactor (von Willebrand factor) as well as activated partial thromboplastin time. Factor VIII coagulant activity should be determined before giving Desmopressin Acetate Injection for hemostasis. If factor VIII coagulant activity is present at less than 5% of normal, Desmopressin Acetate Injection should not be relied on.

von Willebrand’s Disease: Laboratory tests for assessing patient status include levels of factor VIII coagulant activity, factor VIII ristocetin cofactor activity, and factor VIII von Willebrand factor antigen. The skin bleeding time may be helpful in following these patients.

Diabetes

Insipidus: Laboratory tests for monitoring the patient include urine volume and osmolality. In some cases, plasma osmolality may be required.

Drug

Interactions: Although the pressor activity of Desmopressin Acetate Injection is very low compared with the antidiuretic activity, use of doses as large as 0.3 mcg/kg of Desmopressin Acetate Injection with other pressor agents should be done only with careful patient monitoring. The concomitant administration of drugs that may increase the risk of water intoxication with hyponatremia, (e.g., tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine, opiate analgesics, NSAIDs, lamotrigine and carbamazepine) should be performed with caution.

Desmopressin Acetate

Injection has been used with epsilon aminocaproic acid without adverse effects.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Studies with Desmopressin Acetate Injection have not been performed to evaluate carcinogenic potential, mutagenic potential or effects on fertility.

Pregnancy: Fertility studies have not been done. Teratology studies in rats and rabbits at doses from 0.05 to 10 mcg/kg/day (approximately 0.1 times the maximum systemic human exposure in rats and up to 38 times the maximum systemic human exposure in rabbits based on surface area, mg/m 2 ) revealed no harm to the fetus due to Desmopressin Acetate Injection. There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Several publications of desmopressin acetate’s use in the management of diabetes insipidus during pregnancy are available; these include a few anecdotal reports of congenital anomalies and low birth weight babies. However, no causal connection between these events and desmo- pressin acetate has been established. A fifteen year, Swedish epidemiologic study of the use of desmopressin acetate in pregnant women with diabetes insipidus found the rate of birth defects to be no greater than that in the general population; however, the statistical power of this study is low. As opposed to preparations containing natural hormones, desmopressin acetate in antidiuretic doses has no uterotonic action and the physician will have to weigh the therapeutic advantages against the possible risks in each case.

Nursing

Mothers: There have been no controlled studies in nursing mothers. A single study in postpartum women demonstrated a marked change in plasma, but little if any change in assayable Desmopressin Acetate Injection in breast milk following an intranasal dose of 10 mcg. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Desmopressin Acetate Injection is admin- istered to a nursing woman.

Pediatric

Use: 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 .)

Desmopressin Acetate Injection

4 mcg/mL should not be used in infants less than three months of age in the treatment of hemophilia A or von Willebrand’s disease; safety and effectiveness in pediatric patients under 12 years of age with diabetes insipidus have not been established.

Geriatric

Use: Clinical 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 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.

Desmopressin Acetate

Injection is contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50 mL/min). (See CLINICAL PHARMACOLOGY , Human Pharmacokinetics and CONTRAINDICATIONS .) 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 .)

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 USP 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 USP concomitantly with these drugs and when doses of these drugs are increased <span class="opacity-50 text-xs">[see Contraindications (4) , Warnings and Precautions (5.1) , Drug Interactions (7.1) , Use in Specific Populations (8.4 , 8.5) ]</span> .

7.2 Other Vasoconstrictors Desmopressin Acetate Injection USP can elevate blood pressure. Use of Desmopressin Acetate Injection USP with other vasoconstrictors may require a reduction of the Desmopressin Acetate Injection USP dosage <span class="opacity-50 text-xs">[see Warnings and Precautions (5.2) , Adverse Reactions (6) ]</span>.