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Desmopressin: Mechanism, Adverse Effects, Contraindications, and Dosage

Mechanism of Action

Desmopressin, a synthetic analog of vasopressin (antidiuretic hormone, ADH), reduces nocturnal urine production and thereby decreases the frequency of nocturnal enuresis or nocturia. At therapeutic doses, desmopressin has negligible vasopressor activity and therefore does not meaningfully affect smooth muscle tone or blood pressure.

Urological Indications

• Nocturnal enuresis: after nonpharmacologic therapy fails or as an adjunct to behavioral interventions.
• Nocturia: Treatment of idiopathic nocturnal polyuria in adults with at least two nocturnal voids.
• Central diabetes insipidus or other states of ADH deficiency

Pharmacokinetics of Desmopressin

Desmopressin has very low oral bioavailability (well below 1% compared with intravenous administration), with substantial interindividual variability, and a clinically relevant food effect. Sublingual administration is more reliable than conventional oral tablets. After intranasal administration, bioavailability is around 10%. Desmopressin undergoes predominantly renal elimination with an elimination half-life of about 2 to 3 hours in patients with normal kidney function. The antidiuretic effect typically begins about 1 hour after administration and reaches a maximum at approximately 4 to 7 hours. The duration of effect depends on dose and kidney function.

Adverse Effects of Desmopressin

• Headache, abdominal pain, and abdominal cramping.
• Water retention with hyponatremia, especially when patients increase their fluid intake.
• Warning signs include headache, nausea and/or vomiting, unusual fatigue, confusion, or rapid weight gain during desmopressin therapy.
• Severe hyponatremia can result in cerebral edema, seizures, coma, respiratory arrest, or death. Even with appropriate fluid restriction, there is a risk of serious complications.

Contraindications of Desmopressin

• During illnesses that can cause fluid or electrolyte imbalance (e.g., gastroenteritis, systemic infection).
• Hyponatremia or a history of hyponatremia.
• Polydipsia (habitual or psychogenic) or other conditions with excessive fluid intake.
• Moderate to severe renal impairment (creatinine clearance < 50 mL/min).
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH).
• Heart failure, uncontrolled hypertension, treatment with loop diuretics or systemic/inhaled glucocorticoids.
• Use with caution and monitor sodium closely in adults aged 65 years or older.

Pharmacological Interactions of Desmopressin

Medications that promote hyponatremia increase the risk of water retention and hyponatremia during desmopressin therapy. Examples include antidepressants (including selective serotonin reuptake inhibitors), chlorpromazine, carbamazepine, loop diuretics, glucocorticoids, and nonsteroidal anti-inflammatory drugs (NSAIDs). With oral administration, loperamide can increase desmopressin exposure and thereby increase the risk of hyponatremia.

Dosage of Desmopressin

Treatment of Enuresis

Start with 200 μg desmopressin orally at bedtime (0–0–1) for two weeks. If the response is inadequate, increase to 400 μg orally at bedtime (0–0–1) for an additional two weeks. If therapy is effective, continue treatment and then taper desmopressin gradually to reduce relapse.

Consistent fluid restriction is essential to reduce the risk of hyponatremia: limit fluid intake from 1 hour before dosing until 8 hours after dosing, and withhold desmopressin during acute febrile illness, vomiting, or diarrhea. Consider serum sodium testing in patients with symptoms of hyponatremia and in children with risk factors for hyponatremia.

Sublingual Dosing for the Treatment of Nocturia

For women, use 25 μg sublingually once daily; for men, use 50 μg sublingually once daily, taken one hour before bedtime. Follow the fluid restriction recommendations above. Check serum sodium before starting therapy and repeat testing after 3 to 7 days and again after 1 month; monitor more frequently in older adults and in patients with risk factors for hyponatremia.

Treatment of Diabetes Insipidus

Adjust dosing individually based on urine volume, body weight, and serum sodium concentration. A common starting dose in adults is 100 μg orally three times daily or 60 μg sublingually, with subsequent titration to effect. The maintenance dose is usually 300–600 μg/day. Intranasal dosing (for example, 10–20 μg per day) is also possible for central diabetes insipidus, but dosing varies substantially by formulation and patient response.

References

J. Han, J. H. Jung, C. J. Bakker, M. H. Ebell, and P. Dahm, “Desmopressin for treating nocturia in men.,” Cochrane Database Syst Rev, vol. 10, p. CD012059, 2017, doi: 10.1002/14651858.CD012059.pub2.

Schultz-Lampel und Thüroff 2000 SCHULTZ-LAMPEL, D. ; THÜROFF, J. W.: Enuresis und kindliche Harninkontinenz.
In: THÜROFF, JW (Hrsg.) ; SCHULTE-WISSERMANN, H (Hrsg.): Kinderurologie in Klinik und Praxis.
Stuttgart New York : Thieme, 2000, S. 265–275

  Deutsche Version: Mechanismus, Nebenwirkungen und Kontraindikationen von Desmopressin

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