General

**BEERS Drug**

Pronunciation:
des-moe-press-in

Trade Name(s)

• Bipazen 
• DDAVP
• DDAVP Melt 
• Nocdurna
• Octostim 

Ther. Class.

hormones

Pharm. Class.

antidiuretic hormones

Indications

• PO SL SUBQ IV Intranasal Central diabetes insipidus caused by a deficiency of vasopressin.
• IV Bleeding in certain types of hemophilia and von Willebrand disease.
• Intranasal SL Nocturia due to nocturnal polyuria in patients who awaken ≥2 times per night to void (Nocdurna only).
• PO SL Primary nocturnal enuresis.

Action

An analogue of naturally occurring vasopressin (antidiuretic hormone). Primary action is enhanced reabsorption of water in the kidneys.

Therapeutic Effect(s):

• Prevention of nocturnal enuresis.
• Reduction in number of episodes of nocturia.
• Maintenance of appropriate body water content in diabetes insipidus.
• Control of bleeding in certain types of hemophilia or von Willebrand disease.

Pharmacokinetics

Absorption: <1% absorbed following oral or SL administration; 3–4% absorbed following intranasal administration.

Distribution: Distribution not fully known.

Metabolism and Excretion: Primarily excreted in urine.

Half-life: PO:  1.5–2.5 hr;  SL:  2.8 hr;  IV:  75 min (↑ in renal impairment);  Intranasal:  1.8–3.5 hr.

TIME/ACTION PROFILE (PO, intranasal = antidiuretic effect; IV = effect on factor VIII activity)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity;
• Hypersensitivity to chlorobutanol;
• Patients with severe type I, type IIB, or platelet-type (pseudo) von Willebrand disease; hemophilia A with factor VIII levels <5%; or hemophilia B;
• Renal impairment (CCr <50 mL/min);
• Black Box:  Current or a history of hyponatremia;
• Polydipsia;
• Black Box:  Excessive fluid intake, concurrent use of loop diuretics or systemic/inhaled glucocorticoids, or conditions that can lead to electrolyte or fluid imbalances (↑ risk of hyponatremia);
• Known or suspected syndrome of inappropriate antidiuretic hormone secretion;
• HF (New York Heart Association class II–IV);
• Uncontrolled hypertension;
• OB:  Nocdurna not recommended for treatment of nocturia in pregnancy.

Use Cautiously in:

• Angina pectoris;
• Hypertension;
• Patients at risk for hyponatremia;
• Patients at risk for ↑ intracranial hypertension;
• Urinary retention (Nocdurna only);
• Women (↑ risk of hyponatremia; require ↓ dose);
• Patients who require use of other intranasal medications;
• Pedi:  Safety and effectiveness not established in children (Nocdurna only);
• Geri:  Black Box:  Appears on Beers list. ↑ risk of hyponatremia in older adults. Avoid use for treatment of nocturia or nocturnal polyuria in older adults.

Adverse Reactions/Side Effects

CV: edema, hypertension, hypotension, tachycardia (large IV doses only)

Derm: flushing

EENT:  intranasal: epistaxis, nasal congestion, nasal discomfort, rhinitis, sneezing

F and E: hyponatremia

GI: dry mouth, mild abdominal cramps, nausea

GU: vulval pain

Local: phlebitis at IV site

MS: back pain

Neuro: dizziness, drowsiness, headache, listlessness, SEIZURES

Resp: dyspnea

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

•  Loop diuretics,  systemic glucocorticoids, or  inhaled glucocorticoids  ↑ risk of severe hyponatremia; concurrent use contraindicated.
•  Carbamazepine,  chlorpromazine,  lamotrigine,  NSAIDs,  opioids,  SSRIs,  sulfonylureas,  TCAs, or  thiazide diuretics  may ↑ risk of fluid retention and hyponatremia.
•  Demeclocycline,  lithium, or  norepinephrine  may diminish the antidiuretic response to desmopressin.
• Large doses may enhance the effects of  vasopressors.

Route/Dosage

Primary Nocturnal Enuresis

PO (Adults and Children  ≥6 yr): 0.2 mg at bedtime; may be titrated up to 0.6 mg at bedtime to achieve desired response.

SL (Adults and Children): 120 mcg 1 hr before bedtime; may be titrated up to 360 mcg at bedtime to achieve desired response.

Diabetes Insipidus

PO (Adults and Children): 0.05 mg twice daily; adjusted as needed (usual range: 0.1–1.2 mg/day for adults or 0.1–0.8 mg/day for children in 2–3 divided doses).

SL (Adults and Children): 60 mcg 3 times daily; adjusted as needed (usual range: 120–720 mcg/day in 2–3 divided doses).

Intranasal (Adults  and Children ≥12 yr): DDAVP:  5–40 mcg (0.0.05–0.4 mL) in 1–3 divided doses.

Intranasal (Children  3 mo–12 yr): DDAVP:  5–30 mcg (0.05–0.3 mL) in 1–2 divided doses.

SUBQ IV (Adults  and Children ≥12 yr): 2–4 mcg/day in 2 divided doses.

SUBQ IV (Children  <12 yr): 0.1–1 mcg/day in 1–2 divided doses.

Hemophilia A/von Willebrand Disease

IV (Adults and Children  >3 mo): 0.3 mcg/kg, repeated as needed.

Nocturia

SL (Adults): Women:  27.7 mcg 1 hr before bedtime;  Men:  55.3 mcg 1 hr before bedtime.

Availability (generic available)

Tablets: 0.1 mg, 0.2 mg

Sublingual tablet (Nocdurna): 27.7 mcg, 55.3 mcg, 60 mcg , 120 mcg 

Nasal spray: 10 mcg/spray in 5-mL bottle (contains 50 sprays)

Solution for injection: 4 mcg/mL, 15 mcg/mL 

Assessment

• Black Box:  Restrict free water intake and monitor for hyponatremia.
• Assess nasal mucosa for atrophy or acute or chronic rhinitis; dose interruption may be necessary. If nasal mucosal scarring and edema occur (may lead to erratic and unreliable absorption), discontinue and use IV until nasal problems resolve.
• Nocturnal Enuresis: Monitor frequency of enuresis during therapy. Use cautiously in patients at risk for water intoxication with hyponatremia.
•  Nocturia: Assess for possible causes of nocturia (adults who awaken ≥two times per night to void), including excessive fluid intake before bedtime, and address other treatable causes of nocturia.
• Diabetes Insipidus: Assess for symptoms of dehydration (excessive thirst, dry skin and mucous membranes, tachycardia, poor skin turgor). Weigh daily and assess for edema. Closely monitor volume status in patients with New York Heart Association Class I HF.
• Hemophilia:

  Assess for signs of bleeding.

  • Monitor BP and HR during IV infusion.
  • Monitor intake and output and adjust fluid intake (especially in children and older adults) to avoid overhydration.

Lab Test Considerations:

• Do not start or resume intranasal or SL desmopressin unless serum sodium concentration is normal. Measure serum sodium within 7 days and approximately 1 mo after initiating therapy and periodically during treatment. More frequent monitoring in patients ≥65 yr and in patients at ↑ risk of hyponatremia.  If hyponatremia occurs,  may need to temporarily or permanently discontinue desmopressin.
• Monitor renal function in older adults.
• Diabetes insipidus:  Monitor urine osmolality and, in some cases, plasma osmolality during therapy.
• Nocdurna:  Obtain a 24-hr urine collection to confirm diagnosis of nocturnal polyuria before starting therapy.
• Hemophilia:  Monitor levels of factor VIII coagulant activity, factor VIII antigen, factor VIII ristocetin cofactor (von Willebrand factor), and activated partial thromboplastin time (aPTT).  Hemophilia A:  Determine factor VIII coagulant activity before giving desmopressin for hemostasis.  von Willebrand Disease:  Response to therapy may be assessed by blood sample 45–60 min after the completion of infusion; also monitor skin bleeding time. Do not use in patients with type IIB von Willebrand disease; may induce platelet aggregation.

Signs and symptoms of water intoxication include confusion, drowsiness, headache, weight gain, difficulty urinating, seizures, and coma.

• Treatment of overdose includes ↓ dose and, if symptoms are severe, administration of furosemide.

Implementation

• Do not confuse desmopressin with vasopressin.
• IV desmopressin has ten times the antidiuretic effect of intranasal desmopressin.
• PO Begin oral doses 12 hr after last intranasal dose. Monitor response closely.
• SL Administer 1 hr before bedtime. Place tablet under tongue until dissolved completely. Limit fluid intake for ≥1 hr before until 8 hr after administration. Use without fluid restriction may lead to fluid retention and hyponatremia.
• Intranasal 

  If intranasal dose is used preoperatively, administer 2 hr before procedure. Prime nasal spray pump prior to use by pressing down four times; will remain primed for up to 1 wk. Discard after 50 sprays because <10 mcg will be delivered thereafter. Doses <0.1 mL (10 mcg) should be administered with the rhinal tube delivery system. Store upright.

  • Do not use intranasal form for nocturnal enuresis.
• Diabetes Insipidus: Parenteral dose for antidiuretic effect is administered IV push or SUBQ.
• Hemophilia: Parenteral dose for control of bleeding is administered via IV infusion. If used preoperatively, administer 30 min prior to procedure.

Patient/Family Teaching

• Explain purpose and side effects of desmopressin to patient. Teach patient or caregiver of child proper technique for administration based on product prescribed. Counsel patient that fluid restriction is necessary, and give details based on indication and product prescribed. Instruct patient to take missed doses as soon as remembered but not if it is almost time for the next dose. Do not double doses. Advise patient to read  Patient Information  before starting and with each Rx refill in case of changes.
• Nocturia: Instruct patient to place tablet under tongue 1 hr before bedtime and empty bladder immediately before bedtime. Advise patient to limit fluid intake before bedtime and to avoid caffeine and alcohol before bedtime.
• Diabetes Insipidus: If nasal spray is used, prime pump prior to first use by pressing down four times. Caution patient that nasal spray should not be used beyond the labeled number of sprays; subsequent sprays may not deliver accurate dose. Do not attempt to transfer remaining solution to another bottle.
• Advise patient to report symptoms of hyponatremia (headache, feeling restless, drowsiness, muscle cramps, nausea or vomiting, fatigue, dizziness, change in mental condition [hallucinations, confusion, ↓ awareness or alertness]), water intoxication, or fluid retention.
• Advise patient that rhinitis or upper respiratory infection may ↓ effectiveness of intranasal therapy. If ↑ urine output occurs, patient should contact health care provider for dose adjustment.
• Instruct patient to notify health care provider if fever, infection, or diarrhea occurs. May need to hold medication.
• Advise patient to notify health care provider if bleeding is not controlled or if headache, dyspnea, heartburn, nausea, abdominal cramps, vulval pain, or severe nasal congestion or irritation occurs.
• Patients with diabetes insipidus should carry identification at all times describing disease process and medication regimen.
• Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications. Caution patient to avoid concurrent use of alcohol with this medication.
• Rep:  Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

• Decreased frequency of nocturnal enuresis.
• Decrease in urine volume.
• Relief of polydipsia.
• Increased urine osmolality.
• Control of bleeding in hemophilia and von Willebrand disease.
• Reduced frequency of episodes of nocturia.