STIMATE (NEEDS NO REFRIGERATION)
Clinical safety rating
cautionComprehensive clinical and safety monograph for STIMATE (NEEDS NO REFRIGERATION) (STIMATE (NEEDS NO REFRIGERATION)).
Comprehensive clinical and safety monograph for STIMATE (NEEDS NO REFRIGERATION) (STIMATE (NEEDS NO REFRIGERATION)).
Central diabetes insipidus (approved by FDA)Primary nocturnal enuresis (approved by FDA)Hemophilia A with factor VIII deficiency (off-label)von Willebrand disease (type I, some type II and III) (off-label)Nocturia in multiple sclerosis (off-label)Uremic bleeding (off-label)
Desmopressin is a synthetic analogue of vasopressin (antidiuretic hormone) that increases cyclic AMP levels in renal collecting duct cells, enhancing water reabsorption and concentrating urine. It also raises plasma levels of von Willebrand factor and factor VIII by stimulating release from endothelial stores.
| Metabolism | Primarily metabolized by the liver via reduction of the disulfide bridge by glutathione, and to a lesser extent by proteolysis. The metabolite is not active. Excretion: renal (filtration and tubular secretion). |
| Excretion | Renal excretion of intact drug and metabolites accounts for >90% of elimination; biliary/fecal excretion is minimal (<5%). |
| Half-life | Terminal elimination half-life is 2-4 hours (mean 3 hours), which supports a dosing interval of 2-4 hours in clinical use. |
| Protein binding | Plasma protein binding is approximately 50-60%, primarily to albumin and to a lesser extent alpha-1 acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 0.2-0.4 L/kg, indicating moderate distribution into total body water and some tissue binding. |
| Bioavailability | Intranasal: 10-20%; Intravenous: 100%; Sublingual: 5-10%; Oral: <1% (extensive first-pass metabolism). |
| Onset of Action | Intranasal: 10-30 minutes; Intravenous: 1-5 minutes; Sublingual: 15-30 minutes; Oral: 30-60 minutes. |
| Duration of Action | Intranasal/IV: 2-4 hours; Sublingual/Oral: 3-6 hours; duration is dose-dependent and may be prolonged in hepatic impairment. |
| Molecular Weight | 1183.3 |
Intranasal: 1 spray (1.5 mg) into one nostril; may repeat once after 30-60 minutes if needed. Not to exceed 2 doses per bleeding episode.
| Dosage form | SPRAY, METERED |
| Renal impairment | No dose adjustment required for renal impairment. Insufficient data for GFR-based modifications. |
| Liver impairment | No specific Child-Pugh based dose adjustments available. Use with caution in severe hepatic impairment. |
| Pediatric use | Intranasal: <50 kg: 1 spray (1.5 mg) into one nostril; ≥50 kg: same as adult. May repeat once after 30-60 minutes. |
| Geriatric use | No specific dose adjustment recommended. Monitor for adverse effects due to potential comorbidities and concomitant medications. |
| 1st trimester | Desmopressin is not recommended during the first trimester unless clearly needed. Animal studies have not shown teratogenicity, but human data are limited. |
| 2nd trimester | May be used if benefit outweighs risk. Monitor for hyponatremia and fluid imbalance. |
| 3rd trimester | May be used for diabetes insipidus or hemorrhage. Risk of hyponatremia and uterine hypertonus; use with caution. |
Clinical note
Comprehensive clinical and safety monograph for STIMATE (NEEDS NO REFRIGERATION) (STIMATE (NEEDS NO REFRIGERATION)).
| Placental transfer | Limited data suggest minimal placental transfer due to high molecular weight and peptide nature. In vitro studies indicate minimal crossing. |
| Breastfeeding | Desmopressin is excreted into breast milk in small amounts. It is unlikely to cause adverse effects in the infant due to low oral bioavailability. However, caution is advised, and monitoring for excessive thirst or electrolyte imbalance in the infant is recommended. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | Desmopressin is a synthetic analog of vasopressin. Available data in pregnant women are insufficient to determine drug-associated risk of major birth defects and miscarriage. In animal studies, no teratogenic effects were observed at doses up to 100 times the human dose. Desmopressin does not cross the placenta in significant amounts due to its large molecular weight and enzymatic degradation. During the first trimester, theoretical risk of hyponatremia and seizures in the fetus if maternal hyponatremia occurs. In the second and third trimesters, increased uterine contractility has been reported in some cases. Overall, desmopressin is considered low risk, but caution is advised. |
| Fetal Monitoring | Monitor serum sodium levels regularly to detect hyponatremia, especially in patients with increased water intake or during treatment for central diabetes insipidus. In pregnancy, monitor blood pressure and urine output. Assess for signs of fluid overload. Fetal monitoring via ultrasound for growth and amniotic fluid index if used long-term. |
| Fertility Effects | No known adverse effects on human fertility. Desmopressin is used to treat central diabetes insipidus and nocturia, and does not interfere with reproductive hormone axes. Animal studies show no impairment of fertility. |
■ FDA Black Box Warning
WARNING: HYPONATREMIA and SEIZURES. Desmopressin can cause severe hyponatremia, which may be life-threatening if not promptly treated. Seizures have been reported. Risk is increased in patients with fluid or electrolyte imbalances, cystic fibrosis, heart failure, or those on medications that increase hyponatremia risk.
| Serious Effects |
Hypersensitivity to desmopressin or any componentHyponatremiaModerate to severe renal impairment (CrCl <50 mL/min)Syndrome of Inappropriate Antidiuretic Hormone (SIADH)
| Precautions | Hyponatremia and seizures: monitor serum sodium in patients at high risk; avoid excessive fluid intake., Cardiovascular: caution in patients with coronary artery disease or hypertension, as increased blood pressure or ischemia may occur., Fluid retention: avoid in patients with conditions predisposing to fluid overload (e.g., heart failure)., Thrombotic events: use cautiously in patients with risk factors for thrombosis (e.g., advanced atherosclerosis, smoking, oral contraceptives)., Renal impairment: dose reduction may be necessary; monitor renal function., Cystic fibrosis: increased risk of hyponatremia and seizures., Hypersensitivity: anaphylactic reactions reported; discontinue if allergic reaction occurs. |
| Food/Dietary | Avoid high-sodium foods that may increase thirst and fluid intake. Grapefruit juice may increase desmopressin absorption (monitor for enhanced effect). No other significant food interactions. |
| Clinical Pearls | Stimate (desmopressin acetate) is a synthetic analog of vasopressin used for diabetes insipidus and hemophilia A/von Willebrand disease. It causes vasoconstriction and platelet aggregation; monitor for hyponatremia, especially in elderly or patients with fluid intake >2 L/day. Avoid in patients with severe renal impairment (eGFR <50 mL/min). For nocturnal enuresis, restrict fluid 1 hour before and 8 hours after dose. Needs no refrigeration, but store at room temperature (15-30°C). |
| Patient Advice | Do not refrigerate; store at room temperature. · Limit fluid intake for 8 hours after dosing to prevent water intoxication. · Report headache, nausea, confusion, or rapid weight gain (signs of hyponatremia). · If used for bedwetting, take last dose at bedtime and empty bladder before sleep. · Do not use with alcohol or other vasopressin analogs without doctor approval. |
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