Desmopressin Acetate (desmopressin acetate)

Dosage of desmopressin acetate is expressed in terms of the salt.

Desmopressin acetate is administered intranasally, orally, and by subcutaneous injection, direct IV injection, or slow IV infusion.

In vitro studies in human liver microsome preparations indicate desmopressin does not inhibit the human cytochrome P-450 system.

No in vivo interaction studies have been performed with desmopressin injection to date.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Desmopressin/Glucocorticoids

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Glucocorticoids increase the risk of hyponatremia.(1-4)

CLINICAL EFFECTS: Concurrent use of glucocorticoids may increase the risk of hyponatremia with desmopressin.(1-4)

PREDISPOSING FACTORS: Predisposing factors for hyponatremia include: polydipsia, renal impairment (eGFR < 50 ml/min/1.73m2), illnesses that can cause fluid/electrolyte imbalances, age >=65, medications that cause water retention and/or increase the risk of hyponatremia (carbamazepine, chlorpromazine, lamotrigine, loop diuretics, NSAIDs, opioids, SSRIs, thiazide diuretics, and/or tricyclic antidepressants).

PATIENT MANAGEMENT: The concurrent use of systemic or inhaled glucocorticoids with desmopressin is contraindicated.(1-4) Desmopressin may be initiated 3 days or 5 half-lives after glucocorticoid discontinuation, whichever is longer. If concurrent use is deemed medically necessary, make sure serum sodium levels are normal before beginning therapy and consider using the desmopressin nasal 0.83 mcg dose. Consider measuring serum sodium levels more frequently than the recommended intervals of: within 7 days of concurrent therapy initiation, one month after concurrent therapy initiation and periodically during treatment. Counsel patients to report symptoms of hyponatremia, which may include: headache, nausea/vomiting, feeling restless, fatigue, drowsiness, dizziness, muscle cramps, changes in mental state (confusion, decreased awareness/alertness), seizures, coma, and trouble breathing. Counsel patients to limit the amount of fluids they drink in the evening and night-time and to stop taking desmopressin if they develop a stomach/intestinal virus with nausea/vomiting or any nose problems (blockage, stuffy/runny nose, drainage).(1)

DISCUSSION: In clinical trials of desmopressin for the treatment of nocturia, 4 of 5 patients who developed severe hyponatremia (serum sodium <= 125 mmol/L) were taking systemic or inhaled glucocorticoids. Three of these patients were also taking NSAIDs and one was receiving a thiazide diuretic.(2) Drugs associated with hyponatremia may increase the risk, including loop diuretics, carbamazepine, chlorpromazine, glucocorticoids, lamotrigine, NSAIDs, opioids, SSRIs, thiazide diuretics, and/or tricyclic antidepressants.(1,3-4)

Desmopressin/Loop Diuretics

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Loop diuretics increase the risk of hyponatremia.(1-4)

CLINICAL EFFECTS: Concurrent use of loop diuretics may increase the risk of hyponatremia with desmopressin.(1-4)

PREDISPOSING FACTORS: Predisposing factors for hyponatremia include: polydipsia, renal impairment (eGFR < 50 ml/min/1.73m2), illnesses that can cause fluid/electrolyte imbalances, age >=65, medications that cause water retention and/or increase the risk of hyponatremia (carbamazepine, chlorpromazine, glucocorticoids, lamotrigine, NSAIDs, opioids, SSRIs, thiazide diuretics, and/or tricyclic antidepressants).

PATIENT MANAGEMENT: The concurrent use of loop diuretics with desmopressin is contraindicated.(1-4) If concurrent use is deemed medically necessary, make sure serum sodium levels are normal before beginning therapy and consider using the desmopressin nasal 0.83 mcg dose. Consider measuring serum sodium levels more frequently than the recommended intervals of: within 7 days of concurrent therapy initiation, one month after concurrent therapy initiation and periodically during treatment. Counsel patients to report symptoms of hyponatremia, which may include: headache, nausea/vomiting, feeling restless, fatigue, drowsiness, dizziness, muscle cramps, changes in mental state (confusion, decreased awareness/alertness), seizures, coma, and trouble breathing. Counsel patients to limit the amount of fluids they drink in the evening and night-time and to stop taking desmopressin if they develop a stomach/intestinal virus with nausea/vomiting or any nose problems (blockage, stuffy/runny nose, drainage).(1)

DISCUSSION: In clinical trials of desmopressin for the treatment of nocturia, 4 of 5 patients who developed severe hyponatremia (serum sodium <= 125 mmol/L) were taking systemic or inhaled glucocorticoids. Three of these patients were also taking NSAIDs and one was receiving a thiazide diuretic.(2) Drugs associated with hyponatremia may increase the risk, including loop diuretics, carbamazepine, chlorpromazine, glucocorticoids, lamotrigine, NSAIDs, opioids, SSRIs, thiazide diuretics, and/or tricyclic antidepressants.(1,3-4)

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Desmopressin/Agents With Hyponatremia Risk

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Carbamazepine, chlorpromazine, lamotrigine, NSAIDs, opioids, SSRIs, thiazide diuretics, and/or tricyclic antidepressants increase the risk of hyponatremia.(1-3)

CLINICAL EFFECTS: Concurrent use may increase the risk of hyponatremia with desmopressin.(1-3)

PREDISPOSING FACTORS: Predisposing factors for hyponatremia include: polydipsia, renal impairment (eGFR < 50 ml/min/1.73m2), illnesses that can cause fluid/electrolyte imbalances, age >=65, medications that cause water retention and/or increase the risk of hyponatremia (glucocorticoids, loop diuretics).

PATIENT MANAGEMENT: The concurrent use of agents with a risk of hyponatremia with desmopressin may increase the risk of hyponatremia. If concurrent use is deemed medically necessary, make sure serum sodium levels are normal before beginning therapy and consider using the desmopressin nasal 0.83 mcg dose. Consider measuring serum sodium levels more frequently than the recommended intervals of: within 7 days of concurrent therapy initiation, one month after concurrent therapy initiation and periodically during treatment. Counsel patients to report symptoms of hyponatremia, which may include: headache, nausea/vomiting, feeling restless, fatigue, drowsiness, dizziness, muscle cramps, changes in mental state (confusion, decreased awareness/alertness), seizures, coma, and trouble breathing. Counsel patients to limit the amount of fluids they drink in the evening and night-time and to stop taking desmopressin if they develop a stomach/intestinal virus with nausea/vomiting or any nose problems (blockage, stuffy/runny nose, drainage).(1)

DISCUSSION: In clinical trials of desmopressin for the treatment of nocturia, 4 of 5 patients who developed severe hyponatremia (serum sodium <= 125 mmol/L) were taking systemic or inhaled glucocorticoids. Three of these patients were also taking NSAIDs and one was receiving a thiazide diuretic.(2) Drugs associated with hyponatremia may increase the risk, including loop diuretics, carbamazepine, chlorpromazine, glucocorticoids, lamotrigine, NSAIDs, opioids, SSRIs, thiazide diuretics, and/or tricyclic antidepressants.(1,3-4)

*Hypersensitivity to desmopressin acetate or any ingredient in the formulation.

*Moderate to severe renal impairment (creatinine clearance<50 mL/minute).

*Hyponatremia or a history of hyponatremia.

*Known or suspected syndrome of inappropriate antidiuretic hormone (SIADH) secretion (desmopressin injection).

*Polydipsia (desmopressin injection).

*Concomitant use with loop diuretics, or systemic or inhaled glucocorticoids (desmopressin injection).

*Use during illnesses that can cause fluid or electrolyte imbalance (e.g., gastroenteritis, salt-wasting nephropathies, or systemic infection) (desmopressin injection).

*Heart failure (desmopressin injection).

*Uncontrolled hypertension (desmopressin injection).

• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Hyponatremia

• Kidney disease with likely reduction in glomerular filtration rate (GFr)
• Psychogenic polydipsia

• Chronic heart failure
• Coronary artery disease
• Cystic fibrosis
• Hypertension
• Water intoxication

Adverse effects reported in patients administered desmopressin nasal spray include headache, nasal congestion, rhinitis, nosebleed, sore throat, cough, upper respiratory infections, nausea, flushing, and mild abdominal cramps.

Common adverse effects reported in patients administered desmopressin injection include abdominal cramps, burning pain, erythema, facial flushing, fluid retention, headache, hypersensitivity reactions, hypertension, hyponatremia, hyponatremic seizures, hypotension, nausea, swelling, tachycardia, and thrombotic events.

In long-term clinical studies in which patients with diabetes insipidus receiving desmopressin tablet therapy were followed for periods up to 44 months, transient increases in AST (<=1.5 times the upper limit of normal) were occasionally observed; elevated levels returned to the normal range despite continued use of the tablets.

In controlled clinical trials of desmopressin tablets, headache was the only adverse effect occurring in >=3% or more of patients assessed as being probably, possibly, or remotely related to the study medication.

Rare or Very Rare

• Abnormal hepatic function tests
• Anaphylaxis
• Hypertension
• Hyponatremia
• Hypotension
• Seizure disorder
• Water intoxication

Less Frequent

• Abdominal pain with cramps
• Headache disorder
• Nausea

Rare or Very Rare

• Diarrhea
• Disturbance in thinking
• Flushing
• Vulvodynia
• Weight gain

No enhanced messaging available.

Fluid intake should be carefully restricted during desmopressin therapy in pediatric patients to prevent possible hyponatremia and water intoxication; fluid restriction should be discussed with the patient and/or caregiver.

Desmopressin nasal spray is not indicated in pediatric patients less than 4 years of age.

The safety and effectiveness of desmopressin injection have not been established in infants less than 3 months of age with hemophilia A or von Willebrand disease, or pediatric patients less than 12 years of age with diabetes insipidus.

Desmopressin tablets have been used safely for up to 44 months in pediatric patients 4 years of age or older with diabetes insipidus. In younger patients, dosage adjustment of oral desmopressin should be individualized to prevent an excessive decrease in plasma osmolality leading to hyponatremia and possible seizures.

Desmopressin tablets have been used safely for up to 6 months in pediatric patients 6 years of age and older with primary nocturnal enuresis. In patients with primary nocturnal enuresis, desmopressin therapy should be interrupted during acute intercurrent illness characterized by fluid and/or electrolyte imbalance (e.g., systemic infections, fever, recurrent vomiting or diarrhea) and under conditions associated with increased water intake (e.g., extremely hot weather, vigorous exercise).

Extensive experience with desmopressin use in pregnant women over several decades, based on the available published data and case reports, has not demonstrated anassociated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In vitrostudies with human placenta indicate poor placental transfer of desmopressin. Furthermore, reproductive and developmental toxicity studies in pregnant rats and rabbits administered desmopressin during organogenesis found no evidence of adverse developmental effects.

The manufacturer of desmopressin tablets states there are no adequate and controlled studies to date using desmopressin in pregnant females, and the medication should be used during pregnancy only if clearly needed. Although published reports state desmopressin, unlike preparations containing the natural hormones, has no uterotonic effect at usual antidiuretic doses, the clinician must weigh potential therapeutic benefits against possible risks.

Pregnant females with hemophilia A or von Willebrand disease may have an elevated risk of bleeding diatheses and hemorrhagic complications during delivery. Newborns who are affected may also be at increased risk for bleeding diatheses.

Clinically meaningful exposure of breast-fed infants to desmopressin is not expected following maternal administration, as transfer of desmopressin into human breast milk occurs at negligible levels. No data are available regarding effects of desmopressin on the breast-fed infant or on milk production.

When considering use of desmopressin during lactation, weigh developmental and health benefits of breast-feeding against the mother's clinical need for therapy and any potential adverse effects on the breast-fed child from desmopressin or the underlying maternal condition. Caution should be exercised if desmopressin tablets are administered to breast-feeding mothers.

In general, dosage generally should be titrated carefully in geriatric patients, usually initiating therapy at the low end of the dosage range. The greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and other medication therapies that may have interactions or contribute to adverse effects observed in the elderly should be considered.

Desmopressin is known to be substantially excreted by the kidney and risk of severe adverse reactions may be increased in patients with impaired renal function. Because geriatric patients may have age-related decreased renal function, renal function should be monitored and dosage adjusted accordingly.

Use of desmopressin in geriatric patients requires careful fluid intake restriction to prevent possible water intoxication with hyponatremia.

Fluid intake should be carefully restricted during desmopressin therapy in geriatric patients to prevent possible hyponatremia and water intoxication; fluid restriction should be discussed with the patient.

Clinical studies of desmopressin did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients. While other clinical experience has not revealed age-related differences in response, medication dosage generally should be titrated carefully in geriatric patients, usually initiating therapy at the low end of the dosage range. The greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and other medication therapies that may have interactions or contribute to adverse effects observed in the elderly should be considered.

Desmopressin is known to be substantially excreted by the kidney and the risk of severe adverse reactions to the medication may be increased in patients with impaired renal function. Because geriatric patients may have age-related decreased renal function, renal function should be monitored and dosage adjusted accordingly.