Desmotabs Melt 120 micrograms oral lyophilisate

Update to SPC Section 4.8 - Change to HPRA contact details

Update to SPC Section 6.5 - Deletion of 10-tablet pack size

Update to include new HPRA contact information

Update to include new HPRA contact information

SPC unchanged.
Spelling error corrected.

SPC unchanged.
Spelling error corrected.

Section 4.2: section ‘General’ inserted containing the following text:

“Method of administration: Desmotabs Melt is placed under the tongue where it dissolves without the need for water.

 Effect of food: Food intake may reduce the intensity and duration of the antidiuretic effect at low doses of desmopressin (see section 4.5).

 In the event of signs or symptoms of water retention and /or hyponatraemia (headache, nausea/vomiting, weight gain, and, in severe cases, convulsions) treatment should be interrupted until the patient has fully recovered.  When restarting treatment strict fluid restriction should be enforced (see section 4.4).

 If adequate clinical effect is not achieved within 4 weeks following appropriate dose titration the medication should be discontinued.”

 

Section 4.2: ‘Special Population’ section inserted as follows:

“Elderly:

The initiation of treatment in the elderly (patients over 65 years) is contraindicated in patients being treated for nocturia and primary nocturnal enuresis.

Dosage recommendation for elderly suffering from central diabetes insipidus is the same as for other age groups. 

 

Renal Impairment

Desmotabs Melt is contraindicated in case of moderate and severe renal insufficiency (creatinine clearance below 50 ml/min) (see section 4.3).

 

Hepatic Impairment

In vitro human liver microsome metabolism studies of desmopressin have shown that no significant amount is metabolized in the liver by the cytochrome P450 system. Thus human liver metabolism in vivo by the cytochrome P450 system is unlikely to occur. The effect of desmopressin on the pharmacokinetics of other drugs is likely to be minimal due to its lack of inhibition of the cytochrome P450 drug metabolizing system (see section 4.5).

 

Paediatric Population

Desmotabs Melt is indicated in Central Diabetes Insipidus and Primary Nocturnal Enuresis (see section 5.1 and indication specific information in 4.2 above).  Dose recommendations are the same as in adults.”

 

Section 4.4:
-          sentence added: “All patients and, when applicable, their guardians should be carefully instructed to adhere to the fluid restrictions. “
-          two statements added to the section ‘Precautions’:
    o    “Precautions must be taken in patients at risk for increased intracranial pressure.”
    o    “Desmopressin should be used with caution in patients with conditions characterized by fluid and/or electrolyte imbalance”

 

 

Section 4.5:
sentence updated as follows:

“Substances, which are known to induce SIADH, e.g. tricyclic antidepressants, selective serotonine reuptake inhibitors, chlorpromazine and carbamazepine as well as some antidiabetics of the sulfonylurea group particularly Chlorpropamide may cause an additive antidiuretic effect leading to an increased risk of water retention/hyponatraemia (see section 4.4).”

Section 4.6:
-          Sentence updated as follows: “Data on a limited number (n=53) of exposed pregnancies in women with diabetes insipidus as well as data on a limited number (n=54) of exposed pregnancies in women with von Willebrand disease indicate no adverse effects of desmopressin on pregnancy or on the health of the foetus/ newborn child.”

-          New sentences added:
    o    “Caution should be exercised when prescribing Desmotabs Melt to pregnant women.”
    o    “Fertility studies have not been done.  In vitro analysis of human cotyledon models have shown that there is no transplacental transport of desmopressin when administered at therapeutic concentrations corresponding to recommended dose.”

Section 4.8:
Full section update – see SPC for details.

Section 5.1:
Sentence updated as follows: “This results in a considerably longer duration of action and a complete lack of pressor effect in the dosages clinically used. The uterotonic and vasopressor actions are extremely low in the dosages clinical used.”

Section 5.2:
full update, see SPC.

Section 5.3:
Section update as follows: “There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.  Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, toxicity to reproduction. Carcinogenicity studies have not been performed with desmopressin, because it is very closely related to the naturally-occurring peptide hormone.”

Section 4.2: section ‘General’ inserted containing the following text:

“Method of administration: Desmotabs Melt is placed under the tongue where it dissolves without the need for water.

 Effect of food: Food intake may reduce the intensity and duration of the antidiuretic effect at low doses of desmopressin (see section 4.5).

 In the event of signs or symptoms of water retention and /or hyponatraemia (headache, nausea/vomiting, weight gain, and, in severe cases, convulsions) treatment should be interrupted until the patient has fully recovered.  When restarting treatment strict fluid restriction should be enforced (see section 4.4).

 If adequate clinical effect is not achieved within 4 weeks following appropriate dose titration the medication should be discontinued.”

 

Section 4.2: ‘Special Population’ section inserted as follows:

“Elderly:

The initiation of treatment in the elderly (patients over 65 years) is contraindicated in patients being treated for nocturia and primary nocturnal enuresis.

Dosage recommendation for elderly suffering from central diabetes insipidus is the same as for other age groups. 

 

Renal Impairment

Desmotabs Melt is contraindicated in case of moderate and severe renal insufficiency (creatinine clearance below 50 ml/min) (see section 4.3).

 

Hepatic Impairment

In vitro human liver microsome metabolism studies of desmopressin have shown that no significant amount is metabolized in the liver by the cytochrome P450 system. Thus human liver metabolism in vivo by the cytochrome P450 system is unlikely to occur. The effect of desmopressin on the pharmacokinetics of other drugs is likely to be minimal due to its lack of inhibition of the cytochrome P450 drug metabolizing system (see section 4.5).

 

Paediatric Population

Desmotabs Melt is indicated in Central Diabetes Insipidus and Primary Nocturnal Enuresis (see section 5.1 and indication specific information in 4.2 above).  Dose recommendations are the same as in adults.”

 

Section 4.4:
-          sentence added: “All patients and, when applicable, their guardians should be carefully instructed to adhere to the fluid restrictions. “
-          two statements added to the section ‘Precautions’:
    o    “Precautions must be taken in patients at risk for increased intracranial pressure.”
    o    “Desmopressin should be used with caution in patients with conditions characterized by fluid and/or electrolyte imbalance”

 

 

Section 4.5:
sentence updated as follows:

“Substances, which are known to induce SIADH, e.g. tricyclic antidepressants, selective serotonine reuptake inhibitors, chlorpromazine and carbamazepine as well as some antidiabetics of the sulfonylurea group particularly Chlorpropamide may cause an additive antidiuretic effect leading to an increased risk of water retention/hyponatraemia (see section 4.4).”

Section 4.6:
-          Sentence updated as follows: “Data on a limited number (n=53) of exposed pregnancies in women with diabetes insipidus as well as data on a limited number (n=54) of exposed pregnancies in women with von Willebrand disease indicate no adverse effects of desmopressin on pregnancy or on the health of the foetus/ newborn child.”

-          New sentences added:
    o    “Caution should be exercised when prescribing Desmotabs Melt to pregnant women.”
    o    “Fertility studies have not been done.  In vitro analysis of human cotyledon models have shown that there is no transplacental transport of desmopressin when administered at therapeutic concentrations corresponding to recommended dose.”

Section 4.8:
Full section update – see SPC for details.

Section 5.1:
Sentence updated as follows: “This results in a considerably longer duration of action and a complete lack of pressor effect in the dosages clinically used. The uterotonic and vasopressor actions are extremely low in the dosages clinical used.”

Section 5.2:
full update, see SPC.

Section 5.3:
Section update as follows: “There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.  Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, toxicity to reproduction. Carcinogenicity studies have not been performed with desmopressin, because it is very closely related to the naturally-occurring peptide hormone.”

Sec 4.3: Statement added: “Before prescribing Desmotabs Melt the diagnoses of psychogenic polydipsia and alcohol abuse should be excluded.”

 

Sec 4.4: Statement added: “All patients on desmopressin therapy should be observed for the signs of symptoms associated with hyponatraemia (headache, nausea/vomiting, weight increased and, in severe cases, convulsions).”

 

Sec 4.8: Updated to MedDra format

 

Sec 6.3: Shelf-life updated from 3 to 4 years

 

Sec 6.4: Storage conditions updated to “Store in original package in order to protect from light and moisture”.

Sec 4.3: Statement added: “Before prescribing Desmotabs Melt the diagnoses of psychogenic polydipsia and alcohol abuse should be excluded.”

 

Sec 4.4: Statement added: “All patients on desmopressin therapy should be observed for the signs of symptoms associated with hyponatraemia (headache, nausea/vomiting, weight increased and, in severe cases, convulsions).”

 

Sec 4.8: Updated to MedDra format

 

Sec 6.3: Shelf-life updated from 3 to 4 years

 

Sec 6.4: Storage conditions updated to “Store in original package in order to protect from light and moisture”.

Section 6.3.  Shelf life changed from 2 to 3 years

Section 6.3.  Shelf life changed from 2 to 3 years