- Approval Id
- 9e93f53e27e707a6
- Drug Approval Emc Name
- DDAVP Melt 240mcg oral lyophilisate
- Drug Name
- DDAVP Melt 240mcg oral lyophilisate
- Company Address
- Drayton Hall, Church Road, West Drayton, UB7 7PS, UK
- Company Website
- http://www.ferring.co.uk
- Company Telephone
- +44 (0)844 931 0050
- Company Medical Info Email
- medical.uk@ferring.com
- Company Customer Care Direct Line
- 0800 111 4125
- Atc Code
- H01BA02
- Legal Category
- Prescription only medicine
- Authorisation Holder
- Ferring Pharmaceuticals Ltd.Drayton HallChurch RoadWest DraytonUB7 7PSUnited Kingdom
- Authorisation Number
- DDAVP Melt 60 micrograms oral lyophilisate PL 03194/0091DDAVP Melt 120 micrograms oral lyophilisate PL 03194/0092DDAVP Melt 240 micrograms oral lyophilisate PL 03194/0093
- Authorisation Date
- 19th January 2006
- Instruction Authorisation Holder
- Ferring Pharmaceuticals Ltd.Drayton HallChurch RoadWest DraytonUB7 7PSUnited Kingdom
- Instruction Authorisation Number
- DDAVP Melt 60 micrograms oral lyophilisate PL 03194/0091DDAVP Melt 120 micrograms oral lyophilisate PL 03194/0092DDAVP Melt 240 micrograms oral lyophilisate PL 03194/0093
- Instruction Authorisation Date
- 19th January 2006
- Instruction Composition
- Each unit contains 60, 120 or 240 micrograms desmopressin (as acetate).For excipients, see 6.1
- Instruction Dosage Form
- Oral lyophilisateDDAVP Melt 60 micrograms oral lyophilisateWhite, round, oral lyophilisate marked with a drop shaped figure on one side.DDAVP Melt 120 micrograms oral lyophilisateWhite, round, oral lyophilisate marked with two drop shaped figures on one side.DDAVP Melt 240 micrograms oral lyophilisateWhite, round, oral lyophilisate marked with three drop shaped figure on one side.
- Instruction Clinical Particulars
- 4.1 Therapeutic indications
DDAVP Melt is indicated for the treatment of vasopressin-sensitive cranial diabetes insipidus or in the treatment of post-hypophysectomy polyuria/polydipsia.4.2 Posology and method of administration
DDAVP Melt is for sublingual use.
\*\*Treatment of diabetes insipidus:\*\*
Dosage is individual in diabetes insipidus but the total daily sublingual dose normally lies in the range of 120 micrograms to 720 micrograms. A suitable starting dose in adults and children is 60 micrograms three times daily, administered sublingually. This dosage regimen should then be adjusted in accordance with the patient's response. For the majority of patients, the maintenance dose is 60 micrograms to 120 micrograms sublingually three times daily.
\*\*Post-hypophysectomy polyuria/polydipsia:\*\*
The dose of DDAVP Melt should be controlled by measurement of urine osmolality.4.3 Contraindications
DDAVP Melt is contraindicated in cases of cardiac insufficiency and other conditions requiring treatment with diuretic agents.Before prescribing DDAVP Melt, the diagnoses of psychogenic polydipsia and alcohol abuse should be excluded.4.4 Special warnings and precautions for use
Care should be taken with patients who have reduced renal function and/or cardiovascular disease. In chronic renal disease the antidiuretic effect of DDAVP Melt would be less than normal.Precautions to prevent fluid overload must be taken in:- conditions characterised by fluid and/or electrolyte imbalance- patients at risk for increased intracranial pressure.4.5 Interaction with other medicinal products and other forms of interaction
Substances which are known to induce SIADH e.g. tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine and carbamazepine, may cause an additive antidiuretic effect leading to an increased risk of water retention and/or hyponatraemia.NSAIDs may induce water retention and/or hyponatraemia.Concomitant treatment with loperamide may result in a 3-fold increase of desmopressin plasma concentrations, which may lead to an increased risk of water retention and/or hyponatraemia. Although not investigated, other drugs slowing intestinal transport might have the same effect.A standardised 27% fat meal significantly decreased the absorption (rate and extent) of a 0.4mg dose of oral desmopressin tablets. Although it did not significantly affect the pharmacodynamic effect (urine production and osmolality), there is the potential for this to occur at lower doses. If a diminution of effect is noted, then the effect of food should be considered before increasing the dose.4.6. Pregnancy and lactation
\*Pregnancy:\*
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. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development.Caution should be exercised when prescribing to pregnant women. Blood pressure monitoring is recommended due to the increased risk of pre-eclampsia.
\*Lactation:\*
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.4.7 Effects on ability to drive and use machines
None4.8 Undesirable effects
Side-effects include headache, stomach pain and nausea. 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 with desmopressin without concomitant reduction of fluid intake may lead to water retention/hyponatraemia with accompanying symptoms of headache, nausea, vomiting, weight gain, decreased serum sodium and in serious cases, convulsions.4.9 Overdose
An overdose of DDAVP Melt leads to a prolonged duration of action with an increased risk of water retention and/or hyponatraemia.
\*Treatment:\*
Although the treatment of hyponatraemia should be individualised, the following general recommendations can be given. Hyponatraemia is treated by discontinuing the desmopressin treatment, fluid restriction and symptomatic treatment if needed
- Instruction Pharmacology
- 5.1 Pharmacodynamic properties
Pharmacotherapeutic group: vasopressin and analoguesATC code: H01B A02In its main biological effects, DDAVP does not differ qualitatively from vasopressin. However, DDAVP is characterised by a high antidiuretic activity whereas the uterotonic and vasopressor actions are extremely low.5.2 Pharmacokinetic properties
The overall mean systemic bioavailability of desmopressin administered sublingually as Melts at doses of 200, 400 and 800 micrograms is 0.25% with a 95% confidence interval of 0.21% - 0.31%. The Cmax was 14, 30 and 65pg/ml after administration of 200, 400 and 800 micrograms respectively. tmax was observed at 0.5 2.0 hours after dosing. The geometric mean terminal half-life is 2.8 (CV = 24%) hours.Correlation table between desmopressin in Tablet and Melt forms:
| | | | |
| --- | --- | --- | --- |
| \*\*Tablet\*\* | \*\*Tablet\*\* | \*\*Melt\*\* | \*\*Melt\*\* |
| Desmopressin acetate | Desmopressin free base | Desmopressin free base | Desmopressin acetate |
| 0.1mg | 89 micrograms | 60 micrograms | Approx. 67 micrograms + |
| 0.2mg | 178 micrograms | 120 micrograms | Approx. 135 micrograms + |
| 0.4mg | 356 micrograms | 240 micrograms | Approx. 270 micrograms + |
+ calculated for comparative purposesThe distribution volume of desmopressin after intravenous administration is 33 L (0.41 L/kg). Desmopressin does not cross the blood-brain barrier. Desmopressin exhibits a moderate to high variability in bioavailability, both within and between subjects. Concomitant use of food decreases the rate and extent of absorption by 40%.\*In vitro,\* in human liver microsome preparations, it has been shown that no significant amount of desmopressin is metabolised in the liver and thus human liver metabolism \*in vivo\* is not likely to occur.It is unlikely that desmopressin will interact with drugs affecting hepatic metabolism, since desmopressin has been shown not to undergo significant liver metabolism in \*in vitro\* studies with human microsomes. However, formal \*in vivo\* interaction studies have not been performed.5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
- Instruction Pharmaceutical Particulars
- 6.1 List of excipients
GelatinMannitolCitric acid, anhydrous6.2 Incompatibilities
Not applicable6.3 Shelf life
48 months6.4 Special precautions for storage
Store in the original package in order to protect from moisture and light6.5 Nature and contents of container
PVC/Polyamide/Aluminium/Polyamide/PVC blisters. Top foil consists of Paper/Polyester teraphthalate/Aluminium/heat seal lacquer. Strips of 10 oral lyophilisates in packs of 100 oral lyophilisates.6.6 Special precautions for disposal and other handling
None.
- Instruction Content
- ## Composition
Each unit contains 60, 120 or 240 micrograms desmopressin (as acetate).For excipients, see 6.1
## Pharmaceutical Form
Oral lyophilisateDDAVP Melt 60 micrograms oral lyophilisateWhite, round, oral lyophilisate marked with a drop shaped figure on one side.DDAVP Melt 120 micrograms oral lyophilisateWhite, round, oral lyophilisate marked with two drop shaped figures on one side.DDAVP Melt 240 micrograms oral lyophilisateWhite, round, oral lyophilisate marked with three drop shaped figure on one side.
## Clinical Particulars
4.1 Therapeutic indications
DDAVP Melt is indicated for the treatment of vasopressin-sensitive cranial diabetes insipidus or in the treatment of post-hypophysectomy polyuria/polydipsia.4.2 Posology and method of administration
DDAVP Melt is for sublingual use.
\*\*Treatment of diabetes insipidus:\*\*
Dosage is individual in diabetes insipidus but the total daily sublingual dose normally lies in the range of 120 micrograms to 720 micrograms. A suitable starting dose in adults and children is 60 micrograms three times daily, administered sublingually. This dosage regimen should then be adjusted in accordance with the patient's response. For the majority of patients, the maintenance dose is 60 micrograms to 120 micrograms sublingually three times daily.
\*\*Post-hypophysectomy polyuria/polydipsia:\*\*
The dose of DDAVP Melt should be controlled by measurement of urine osmolality.4.3 Contraindications
DDAVP Melt is contraindicated in cases of cardiac insufficiency and other conditions requiring treatment with diuretic agents.Before prescribing DDAVP Melt, the diagnoses of psychogenic polydipsia and alcohol abuse should be excluded.4.4 Special warnings and precautions for use
Care should be taken with patients who have reduced renal function and/or cardiovascular disease. In chronic renal disease the antidiuretic effect of DDAVP Melt would be less than normal.Precautions to prevent fluid overload must be taken in:- conditions characterised by fluid and/or electrolyte imbalance- patients at risk for increased intracranial pressure.4.5 Interaction with other medicinal products and other forms of interaction
Substances which are known to induce SIADH e.g. tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine and carbamazepine, may cause an additive antidiuretic effect leading to an increased risk of water retention and/or hyponatraemia.NSAIDs may induce water retention and/or hyponatraemia.Concomitant treatment with loperamide may result in a 3-fold increase of desmopressin plasma concentrations, which may lead to an increased risk of water retention and/or hyponatraemia. Although not investigated, other drugs slowing intestinal transport might have the same effect.A standardised 27% fat meal significantly decreased the absorption (rate and extent) of a 0.4mg dose of oral desmopressin tablets. Although it did not significantly affect the pharmacodynamic effect (urine production and osmolality), there is the potential for this to occur at lower doses. If a diminution of effect is noted, then the effect of food should be considered before increasing the dose.4.6. Pregnancy and lactation
\*Pregnancy:\*
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. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development.Caution should be exercised when prescribing to pregnant women. Blood pressure monitoring is recommended due to the increased risk of pre-eclampsia.
\*Lactation:\*
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.4.7 Effects on ability to drive and use machines
None4.8 Undesirable effects
Side-effects include headache, stomach pain and nausea. 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 with desmopressin without concomitant reduction of fluid intake may lead to water retention/hyponatraemia with accompanying symptoms of headache, nausea, vomiting, weight gain, decreased serum sodium and in serious cases, convulsions.4.9 Overdose
An overdose of DDAVP Melt leads to a prolonged duration of action with an increased risk of water retention and/or hyponatraemia.
\*Treatment:\*
Although the treatment of hyponatraemia should be individualised, the following general recommendations can be given. Hyponatraemia is treated by discontinuing the desmopressin treatment, fluid restriction and symptomatic treatment if needed
## Pharmacological Properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: vasopressin and analoguesATC code: H01B A02In its main biological effects, DDAVP does not differ qualitatively from vasopressin. However, DDAVP is characterised by a high antidiuretic activity whereas the uterotonic and vasopressor actions are extremely low.5.2 Pharmacokinetic properties
The overall mean systemic bioavailability of desmopressin administered sublingually as Melts at doses of 200, 400 and 800 micrograms is 0.25% with a 95% confidence interval of 0.21% - 0.31%. The Cmax was 14, 30 and 65pg/ml after administration of 200, 400 and 800 micrograms respectively. tmax was observed at 0.5 2.0 hours after dosing. The geometric mean terminal half-life is 2.8 (CV = 24%) hours.Correlation table between desmopressin in Tablet and Melt forms:
| | | | |
| --- | --- | --- | --- |
| \*\*Tablet\*\* | \*\*Tablet\*\* | \*\*Melt\*\* | \*\*Melt\*\* |
| Desmopressin acetate | Desmopressin free base | Desmopressin free base | Desmopressin acetate |
| 0.1mg | 89 micrograms | 60 micrograms | Approx. 67 micrograms + |
| 0.2mg | 178 micrograms | 120 micrograms | Approx. 135 micrograms + |
| 0.4mg | 356 micrograms | 240 micrograms | Approx. 270 micrograms + |
+ calculated for comparative purposesThe distribution volume of desmopressin after intravenous administration is 33 L (0.41 L/kg). Desmopressin does not cross the blood-brain barrier. Desmopressin exhibits a moderate to high variability in bioavailability, both within and between subjects. Concomitant use of food decreases the rate and extent of absorption by 40%.\*In vitro,\* in human liver microsome preparations, it has been shown that no significant amount of desmopressin is metabolised in the liver and thus human liver metabolism \*in vivo\* is not likely to occur.It is unlikely that desmopressin will interact with drugs affecting hepatic metabolism, since desmopressin has been shown not to undergo significant liver metabolism in \*in vitro\* studies with human microsomes. However, formal \*in vivo\* interaction studies have not been performed.5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
## Pharmaceutical Particulars
6.1 List of excipients
GelatinMannitolCitric acid, anhydrous6.2 Incompatibilities
Not applicable6.3 Shelf life
48 months6.4 Special precautions for storage
Store in the original package in order to protect from moisture and light6.5 Nature and contents of container
PVC/Polyamide/Aluminium/Polyamide/PVC blisters. Top foil consists of Paper/Polyester teraphthalate/Aluminium/heat seal lacquer. Strips of 10 oral lyophilisates in packs of 100 oral lyophilisates.6.6 Special precautions for disposal and other handling
None.
- Company Detail Path
- /organization/ferring-pharmaceuticals-inc
