DES-PRESS Nasal Spray
Desmopressin Intranasal Solution BP
For the use of a Registered Medical Practitioner Only.
Desmopressin Intranasal Solution BP
Each Spray Delivers:
Desmopressin Acetate 10 mcg
Eq. to Desmopressin BP 8.9 mcg
Desmopressin Acetate 0.01% w/v
Eq. to Desmopressin BP 0.0089%w/v
Benzalkonium chloride Solution BP 0.02% w/v
(3-Sulphanylpropanoyl)-L-tyrosyl-L-phenylalanyl-L-glutaminyl-L-asparaginyl-L- cysteinyl-L-prolyl-D-arginylglycinamide cyclic (1à6)-disulfide.
Synthetic cyclic nonapeptide, available as acetate.
Desmopressin (as Desmopressin acetate) is a synthetic analogue of the natural pituitary hormone 8-arginine vasopressin (ADH), an antidiuretic hormone affecting renal water conservation.
DES-PRESS Nasal Spray is provided as an aqueous solution for intranasal use.
The DES-PRESS Nasal Spray compression pump delivers 0.1 ml (10 mcg) of Desmopressin (as desmopressin acetate) per spray.
DES-PRESS contains as active substance desmopressin acetate, a synthetic analogue of the natural hormone arginine vasopressin. One mL (0.1 mg) of intranasal DES-PRESS has an antidiuretic activity of about 400 IU; 10 mcg of desmopressin acetate is equivalent to 40 IU.
The biphasic half-lives for intranasal Desmopressin were 7.8 and 75.5 minutes for the fast and slow phases, compared with 2.5 and 14.5 minutes for lysine vasopressin, another form of the hormone used in this condition. As a result, intranasal Desmopressin provides a prompt onset of antidiuretic action with a long duration after each administration.
Desmopressin is a structural analogue of vasopressin, with two chemical changes, namely deamination of the N-terminal and replacement of the 8-L-Arginine by D-8-Arginine. These changes have increased the antidiuretic activity and prolonged the duration of action. The pressor activity is reduced to less than 0.01% and has resulted in a decreased vasopressor action and decreased actions on visceral smooth muscle relative to the enhanced antidiuretic activity, so that clinically effective antidiuretic doses are usually below threshold levels for effects on vascular or visceral smooth muscle. Desmopressin administered intranasally has an antidiuretic effect about one-tenth that of an equivalent dose administered by injection.
Human Pharmacokinetics: Following intranasal administration, the bioavailability of desmopressin is of the order of 10%. Pharmacokinetic parameters following intravenous administration have been reported as follows: Total clearance: 2.6ml/ min/kg body wt. T½: 55mins. Desmopressin 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 (2mcg) injection demonstrated a difference in Desmopressin 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 Cranial Diabetes Insipidus: Desmopressin Intranasal Spray is indicated as antidiuretic replacement therapy in the management of central cranial diabetes insipidus and for management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region. It is ineffective for the treatment of nephrogenic diabetes insipidus.
The use of Desmopressin Intranasal Spray in patients with an established diagnosis will result in a reduction in urinary output with increase in urine osmolality and a decrease in plasma osmolality. This will allow the resumption of a more normal life-style with a decrease in urinary frequency and nocturia.
There are reports of an occasional change in response with time, usually greater than 6 months. Some patients may show a decreased responsiveness, others a shortened duration of effect. There is no evidence this effect is due to the development of binding antibodies but may be due to a local inactivation of the peptide.
Patients are selected for therapy by establishing the diagnosis by means of the water deprivation test, the hypertonic saline infusion test, and/or the response to antidiuretic hormone. Continued response to intranasal Desmopressin can be monitored by urine volume and osmolality.
Desmopressin Nasal Spray is contraindicated in individuals with syndrome of inappropriate ADH secretion (SIADH).
Desmopressin is contraindicated in patients with a history of known or suspected cardiac insufficiency and other conditions requiring treatment with diuretics.
- For intranasal use only.
- When Desmopressin Nasal Spray is prescribed, it is recommended:
- to start at the lowest dose
- to ensure compliance with fluid restriction instructions
- to increase dosage progressively, with caution
- to ensure that in children, administration is under adult supervision in order to control the dose intake.
- Care should be taken with patients who have reduced renal function and/or cardiovascular disease or cystic fibrosis.
- Severe bladder dysfunction and outlet obstruction should be considered before starting treatment.
- Desmopressin Nasal Spray should only be used in patients where orally administered formulations are not feasible.
- Very rare cases of hyponatremia have been reported from world-wide post marketing experience in patients treated with Desmopressin (desmopressin acetate). Desmopressin Nasal Spray 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.
- When Desmopressin Nasal Spray is administered, in particular in pediatric and geriatric patients, fluid intake should be adjusted downward in order to decrease the potential occurrence of water intoxication and hyponatremia (See PRECAUTIONS, Pediatric Use and Geriatric Use.)
- All patients receiving Desmopressin Nasal Spray therapy should be observed for the following signs or 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.
- Desmopressin Nasal Spray 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.
General: Desmopressin Nasal Spray at high dosage has infrequently produced a slight elevation of blood pressure, which disappeared with a reduction in dosage. The drug should be used with caution in patients with coronary artery insufficiency and/or hypertensive cardiovascular disease because of possible rise in blood pressure.
Desmopressin Nasal Spray 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. Anaphylaxis has been reported rarely with intravenous and intranasal administration of Desmopressin.
Central Cranial Diabetes Insipidus: Since Desmopressin is used intranasally, changes in the nasal mucosa such as scarring, edema, or other disease may cause erratic, unreliable absorption in which case intranasal Desmopressin should not be used. For such situations, Desmopressin Injection should be considered.
Information for Patients: Ensure that in children administration is with adult supervision in order to control the dose intake. Patients should be informed that the Desmopressin Nasal Spray bottle accurately delivers 50 doses of 10 mcg each. Any solution remaining after 50 doses should be discarded since the amount delivered thereafter may be substantially less than 10 mcg of drug.
No attempt should be made to transfer remaining solution to another bottle. Patients should be instructed to read accompanying directions on use of the spray pump carefully before use.
Fluid intake should be adjusted downward based upon discussion with the physician.
Laboratory Tests: Laboratory tests for following the patient with central cranial diabetes insipidus or post-surgical or head trauma-related polyuria and polydipsia include urine volume and osmolality. In some cases plasma osmolality measurements may be required.
Drug Interactions: Although the pressor activity of Desmopressin is very low compared to the antidiuretic activity, use of large doses of intranasal Desmopressin with other pressor agents should only be done with careful patient monitoring. The concomitant administration of drugs that may increase the risk of water intoxication with hyponatremia, (e.g. tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine, opiate analgesics, NSAIDs, lamotrigine and carbamazepine) should be performed with caution.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Studies with Desmopressin have not been performed to evaluate carcinogenic potential, mutagenic potential or effects on fertility.
Pregnancy: Category B: Fertility studies have not been done. Teratology studies in rats and rabbits at doses from 0.05 to 10 mcg/kg/day (approximately 0.1 times the maximum systemic human exposure in rats and up to 38 times the maximum systemic human exposure in rabbits based on surface area, mg/m 2) revealed no harm to the fetus due to Desmopressin (desmopressin acetate). Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development.
Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
There are, however, no adequate and well controlled studies in pregnant women.
Several publications of desmopressin acetate’s use in the management of diabetes insipidus during pregnancy are available; these include a few anecdotal reports of congenital anomalies and low birth weight babies. However, no causal connection between these events and desmopressin acetate has been established. A fifteen year Swedish epidemiologic study of the use of desmopressin acetate in pregnant women with diabetes insipidus found the rate of birth defects to be no greater than that in the general population; however, the statistical power of this study is low. As opposed to preparations containing natural hormones, desmopressin acetate in antidiuretic doses has no uterotonic action and the physician will have to weigh the therapeutic advantages against the possible risks in each case.
Data on a limited number (n=53) of exposed pregnancies in women with diabetes insipidus indicate rare cases of malformations in children treated during pregnancy. To date, no other relevant epidemiological data are available.
Nursing Mothers: There have been no controlled studies in nursing mothers. A single study in a post-partum woman demonstrated a marked change in plasma, but little if any change in assayable Desmopressin in breast milk following an intranasal dose of 10 mcg.
Results from analyses of milk from nursing mothers receiving high dose desmopressin (300 micrograms intranasally) indicate that the amounts of desmopressin that may be transferred to the child are considerably less than the amounts required to influence diuresis.
Caution should be exercised when Desmopressin is administered to a nursing woman.
Pediatric Use: Central Cranial Diabetes Insipidus: Desmopressin Nasal Spray has been used in children with diabetes insipidus. Use in infants and children will require careful fluid intake restriction to prevent possible hyponatremia and water intoxication. (See WARNINGS.) The dose must be individually adjusted to the patient with attention in the very young to the danger of an extreme decrease in plasma osmolality with resulting convulsions. Dose should start at 0.05 ml or less. Since the spray cannot deliver less than 0.1 mL (10 mcg), smaller doses should be administered using the rhinal tube delivery system. Do not use the nasal spray in pediatric patients requiring less than 0.1 mL (10 mcg) per dose.
Geriatric Use: Clinical studies of Desmopressin Nasal Spray did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Other reported clinical experience has not identified differences in responses between the elderly and younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or drug therapy.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Desmopressin is contraindicated in patients with moderate to severe renal impairment (defined as a creatinine clearance below 50ml/min). (See CLINICAL PHARMACOLOGY, Human Pharmacokinetics and CONTRAINDICATIONS.)
Use of Desmopressin Nasal Spray in geriatric patients will require careful fluid intake restriction to prevent possible hyponatremia and water intoxication. (See WARNINGS).
There are reports of an occasional change in response with time, usually greater than 6 months.
Some patients may show a decreased responsiveness, others a shortened duration of effect. There is no evidence this effect is due to the development of binding antibodies but may be due to a local inactivation of the peptide.
Side-effects include headache, stomach pain, nausea, nasal congestion, rhinitis and epistaxis. Isolated cases of allergic skin reactions and more severe general allergic reactions have been reported. Very rare cases of emotional disorders including aggression in children have been reported. Treatment without concomitant reduction of fluid intake may lead to water retention/hyponatraemia with or without accompanying warning signs and symptoms (headache, nausea/vomiting, weight gain, decreased serum sodium and in severe cases, convulsions).
Post Marketing: There have been rare reports of hyponatremic convulsions associated with concomitant use with the following medications: oxybutinin and imipramine. See WARNINGS for the possibility of water intoxication and hyponatremia.
An overdose of Desmopressin leads to a prolonged duration of action with an increased risk of water retention and/or hyponatraemia. Signs of overdose may include confusion, drowsiness, continuing headache, problems with passing urine and rapid weight gain due to fluid retention. (See WARNINGS.) In case of overdosage, the dose should be reduced, frequency of administration decreased, or the drug withdrawn according to the severity of the condition. There is no known specific antidote for desmopressin acetate or Desmopressin Nasal Spray. An oral LD50 has not been established. An intravenous dose of 2 mg/kg in mice demonstrated no effect.
DOSAGE AND ADMINISTRATION
Central Cranial Diabetes Insipidus: DES-PRESS Nasal Spray dosage must be determined for each individual patient and adjusted according to the diurnal pattern of response. Response should be estimated by two parameters: adequate duration of sleep and adequate, not excessive, water turnover. Patients with nasal congestion and blockage have often responded well to intranasal Desmopressin.
The usual dosage range in adults is 0.1 to 0.4 mL daily, either as a single dose or divided into two or three doses. Most adults require 0.2 mL daily in two divided doses. The morning and evening doses should be separately adjusted for an adequate diurnal rhythm of water turnover.
For children aged 3 months to 12 years, the usual dosage range is 0.05 to 0.3 mL daily, either as a single dose or divided into two doses.
About 1/4 to 1/3 of patients can be controlled by a single daily dose of Desmopressin administered intranasally. Fluid restriction should be observed. (See WARNINGS, PRECAUTIONS, Pediatric Use and Geriatric Use). The nasal spray pump can only deliver doses of 0.1 mL (10 mcg) or multiples of 0.1 mL. If doses other than these are required, the rhinal tube delivery system may be used. The spray pump must be primed prior to the first use. To prime pump, press down four times. The bottle will now deliver 10 mcg of drug per spray. Discard Desmopressin Nasal Spray after 50 sprays since the amount delivered thereafter per spray may be substantially less than 10 µg of drug.
Geriatric Use: This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. (See CLINICAL PHARMACOLOGY, Human Pharmacokinetics, CONTRAINDICATIONS, and PRECAUTIONS, Geriatric Use)
6 mL bottle with spray pump delivering 60 sprays of 10 mcg.
STORAGE & HANDLING.
Desmopressin Intranasal Solution should be protected from light and stored at a temperature of 2° to 8°,
Keep out of reach of children.
24 Months from the date of manufacturing.
Last Update: May 2011.