Desmopressin Acetate (Page 2 of 4)

Primary Nocturnal Enuresis

Two double-blind, randomized, placebo-controlled studies were conducted in 340 patients with primary nocturnal enuresis. Patients were 5 to 17 years old, and 72% were males. A total of 329 patients were evaluated for efficacy. Patients were evaluated over a two-week baseline period in which the average number of wet nights was 10 (range 4 to 14). Patients were then randomized to receive 0.2, 0.4, or 0.6 mg of desmopressin acetate or placebo. The pooled results after two weeks are shown in the following table:

Response to Desmopressin Acetate and Placebo at Two Weeks of Treatment Mean (SE) Number of Wet Nights/2 Weeks

Placebo (n = 85)

0.2 mg/day (n = 79)

0.4 mg/day (n = 82)

0.6 mg/day (n = 83)

Baseline

10 (0.3)

11 (0.3)

10 (0.3)

10 (0.3)

Reduction from Baseline

1 (0.3)

3 (0.4)

3 (0.4)

4 (0.4)

Percent Reduction from Baseline

10%

27%

30%

40%

p-value vs placebo

—-

< 0.05

< 0.05

< 0.05

Patients treated with desmopressin acetate tablets showed a statistically significant reduction in the number of wet nights compared to placebo-treated patients. A greater response was observed with increasing doses up to 0.6 mg.

In a six month, open-label extension study, patients completing the placebo-controlled studies were started on 0.2 mg/day desmopressin acetate, and the dose was progressively increased until the optimal response was achieved (maximum dose 0.6 mg/day). A total of 230 patients were evaluated for efficacy; the average number of wet nights/2 weeks during the untreated baseline period was 10 (range 4 to 14), and the average duration (SD) of treatment was 4.2 (1.8) months. Twenty-five (25) patients (11%) achieved a complete or near complete response (≤ 2 wet nights/2 weeks) and did not require titration to the 0.6 mg/day dose. The majority of patients (198 of 230, 86%) were titrated to the highest dose. When all dose groups were combined, 128 (56%) showed at least a 50% reduction from baseline in the number of wet nights/2 weeks, while 87 (38%) patients achieved a complete or near complete response.

Human Pharmacokinetics

Desmopressin acetate is mainly excreted in the urine. A pharmacokinetic study conducted in healthy volunteers and patients with mild, moderate, and severe renal impairment (n = 24, 6 subjects in each group) receiving single dose desmopressin acetate (2 mcg) injection demonstrated a difference in desmopressin acetate terminal half-life. Terminal half-life significantly increased from 3 hours in normal healthy patients to 9 hours in patients with severe renal impairment (see CONTRAINDICATIONS).

INDICATIONS AND USAGE

Central Diabetes Insipidus

Desmopressin acetate tablets are indicated as antidiuretic replacement therapy in the management of central diabetes insipidus and for the management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region. Desmopressin acetate is ineffective for the treatment of nephrogenic diabetes insipidus.

Patients were selected for therapy based on the diagnosis by means of the water deprivation test, the hypertonic saline infusion test, and/or response to antidiuretic hormone. Continued response to desmopressin acetate can be monitored by measuring urine volume and osmolality.

Primary Nocturnal Enuresis

Desmopressin acetate tablets are indicated for the management of primary nocturnal enuresis. Desmopressin acetate may be used alone or as an adjunct to behavioral conditioning or other non-pharmacologic intervention.

CONTRAINDICATIONS

Desmopressin acetate tablets are contraindicated in individuals with known hypersensitivity to desmopressin acetate or to any of the components of desmopressin acetate tablets.

Desmopressin acetate tablets are contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50 mL/min).

Desmopressin acetate tablets are contraindicated in patients with hyponatremia or a history of hyponatremia.

WARNINGS

  1. Very rare cases of hyponatremia have been reported from world-wide postmarketing experience in patients treated with desmopressin acetate. Desmopressin acetate is a potent antidiuretic which, when administered, may lead to water intoxication and/or hyponatremia. Unless properly diagnosed and treated hyponatremia can be fatal. Therefore, fluid restriction is recommended and should be discussed with the patient and/or guardian. Careful medical supervision is required.
  2. When desmopressin acetate tablets are administered, in particular in pediatric and geriatric patients, fluid intake should be adjusted downward to decrease the potential occurrence of water intoxication and hyponatremia (see PRECAUTIONS , Pediatric Use and Geriatric Use). All patients receiving desmopressin acetate therapy should be observed for the following signs of symptoms associated with hyponatremia: headache, nausea/vomiting, decreased serum sodium, weight gain, restlessness, fatigue, lethargy, disorientation, depressed reflexes, loss of appetite, irritability, muscle weakness, muscle spasms or cramps and abnormal mental status such as hallucinations, decreased consciousness and confusion. Severe symptoms may include one or a combination of the following: seizure, coma and/or respiratory arrest. Particular attention should be paid to the possibility of the rare occurrence of an extreme decrease in plasma osmolality that may result in seizures which could lead to coma.
  3. Desmopressin acetate should be used with caution in patients with habitual or psychogenic polydipsia who may be more likely to drink excessive amounts of water, putting them at greater risk of hyponatremia.

PRECAUTIONS

General

Intranasal formulations of desmopressin acetate at high doses and desmopressin acetate injection have infrequently produced a slight elevation of blood pressure which disappears with a reduction of dosage. Although this effect has not been observed when single oral doses up to 0.6 mg have been administered, the drug should be used with caution in patients with coronary artery insufficiency and/or hypertensive cardiovascular disease, because of a possible rise in blood pressure.

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.

Rare severe allergic reactions have been reported with desmopressin acetate. Anaphylaxis has been reported rarely with intravenous and intranasal administration of desmopressin acetate but not with desmopressin acetate tablets.

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