Desmopressin 120 micrograms sublingual tablets

Sublingual tablet White or almost white, octagonal, biconvex tablet debossed with 'II' on one side and plain on other side, with 6.5 mm length/width and 2 mm thickness.

4.1 Therapeutic indications Desmopressin 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 Desmopressin 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 Desmopressin should be controlled by measurement of urine osmolality.4.3 Contraindications Desmopressin is contraindicated in cases of cardiac insufficiency and other conditions requiring treatment with diuretic agents. Before prescribing Desmopressin, 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 Desmopressin 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. Excipients with known effect Desmopressin 120 micrograms sublingual tablet contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine This medicinal product contains less than 1 mmol sodium (23 mg) per sublingual tablet, that is to say essentially 'sodium-free'.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 Fertility, 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. Reporting of suspected side effects Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.4.9 Overdose An overdose of Desmopressin 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.

5.1 Pharmacodynamic properties Pharmacotherapeutic group: vasopressin and analogues ATC code: H01B A02 In its main biological effects, Desmopressin does not differ qualitatively from vasopressin. However, Desmopressin 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 Desmopressin sublingual tablets 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 Sublingual Tablet: | | | | | | --- | --- | --- | --- | | Tablet | Tablet | Sublingual tablet | Sublingual tablet | | 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 purposes The 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 Summary of Product Characteristics.

6.1 List of excipients Lactose monohydrate Maize starch Citric acid (E 330) Croscarmellose sodium (E 468) Magnesium stearate (E 470b)6.2 Incompatibilities Not applicable.6.3 Shelf life 30 months6.4 Special precautions for storage *For blisters* Store in the original blister in order to protect from moisture. This medicinal product does not require any special temperature storage conditions. *For HDPE bottles* Store in the original package. Keep the bottle tightly closed in order to protect from moisture. Do not store above 30 ° C.6.5 Nature and contents of container Carton box containing OPA/Al/PVC/PE-AL-AL standard blisters or unit dose blisters with integrated desiccant layer with 10 tablets each. Pack sizes of 10, 30, 60, 90 and 100 sublingual tablets. HDPE bottles with PP caps with integrated desiccant containing 30 or 100 sublingual tablets. Not all pack sizes may be marketed.6.6 Special precautions for disposal and other handling Any unused medicinal product or waste material should be disposed of in accordance with local requirements.