OCTOSTIM

Octostim 15 micrograms/ml Solution for injection

1 ml solution for injection contains 15 micrograms desmopressin acetate equivalent to 13.4 micrograms desmopressin.

For a full list of excipients, see section6.1.

Solution for injection

Uncoloured glassampoule containing a clear aqueous solution.

OCTOSTIM^® solution for subcutaneous injection or as intravenous infusion as follows:

§ For short-term use to increase factor eight levels in patients with mild to moderate haemophilia or von Willebrand's disease under going surgery or following trauma, and who respond positively to a test dose.

§ To test for Fibrinolytic response.

0.3 micrograms/kg body weight subcutaneously or diluted in physiological saline to 50-100 ml and given as an intravenous infusion over 15-30 minutes. If a positive effect is obtained, the initial OCTOSTIM dose may be repeated 1-2 times with intervals of 6-12 hours. Further repetition of the dose may result in a reduced effect.

In patients with haemophilia A the desired increase of VIII:C is appraised by the same criterion as in the treatment with Factor VIII-concentrate. If the OCTOSTIM infusion does not lead to the desired increase of the concentration of VIII:C in plasma, the treatment may be complemented with administration of factor VIII concentrate. Treatment of haemophilia patients should be conducted in consultation with each patient’s coagulation laboratory.

Determination of coagulation factors and bleeding time before OCTOSTIM-treatment:

Plasma levels of VIII:C and vWF:Ag increase substantially after the desmopressin administration. However it has not been possible to establish any correlation between the plasma concentration of these factors and the bleeding time, either before or after desmopressin. The effect of Desmopressin on the bleeding time should therefore, if possible, be tested in the individual patient.

The bleeding time should be as standardised as possible, e.g. with the use of Simplate II. Determination of bleeding time and plasma levels of the coagulation factors should be conducted in co-operation or consultation with a coagulation laboratory.

Treatment control

The VIII:C concentration must be monitored regularly since in a few cases the effect has been seen to decrease with repeated doses.

In connection with administration of OCTOSTIM the patient’s blood pressure must be monitored carefully.

The injection is administered by subcutaneous injection or intravenous infusion. For intravenous infusion the dose (0.3 micrograms/kg body weight) should be diluted in 50-100ml 0.9% sodium chloride for injection (physiological saline) and given over 15-30 minutes.

OCTOSTIM solution for injection is contraindicated in cases of:

- Habitual and psychogenic polydipsia (resulting in a urine production exceeding 40ml/kg/24 hours).

- History of unstable angina pectoris and/or known or suspected cardiac insufficiency and other conditions requiring treatment with diuretics.

- Known hyponatraemia.

- Von Willebrand's Disease Type IIB.

Fibrinolytic response testing should not be carried out in patients with hypertension, heart disease, cardiac insufficiency and other conditions requiring treatment with diuretic agents.

OCTOSTIM solution for injection should be used with caution in:

§ Very young or elderly patients.

§ Conditions characterised by fluid and/or electrolyte imbalance.

§ Patients at risk for increased intracranial pressure.

Measures to prevent fluid overload must be taken in patients with conditions requiring treatment with diuretic agents.

Special warnings:

Special attention must be paid to the risk of fluid retention/hyponatraemia. The fluid intake should be restricted to the least possible and the body weight should be checked regularly. If there is a gradual increase of body weight, decrease of serum sodium to below 130 mmol/l or plasma osmolality to below 270 mOsm/kg body weight, the fluid intake must be reduced drastically and the administration of OCTOSTIM interrupted.

OCTOSTIM does not reduce prolonged bleeding time in thrombocytopenia.

Precautions:

Treatment with Desmopressin should be reassessed during acute intercurrent illnesses and the fluid and electrolyte balance should be carefully monitored, especially in situations with excessive bleeding.

Substances which are known or suspected to induce Syndrome of Inappropriate Antidiuretic Hormone (SIADH) e.g. tricyclic antidepressants, selective serotonin reuptake inhibitors, chlorpromazine and carbamazepine, may cause an additive antidiuretic effect and increase the risk of fluid retention/hyponatraemia. (see 4.4 special Warnings ands Precautions for use).

Non steroidal anti-inflammatory drugs (NSAIDs) may induce fluid retention/hyponatraemia (see section 4.4 special Warnings ands Precautions for use).

Pregnancy:

Published data on a limited number (n=53) of exposed pregnancies in women with diabetes insipidus indicate no adverse effects of desmopressin on pregnancy or on the health of the foetus/newborn child. To date, no other relevant epidemiological data are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.

Caution should be exercised when prescribing to pregnant women.

Lactation:

Results from analyses of milk from nursing mothers receiving a high dose of desmopressin ( 300 micrograms intranasally), indicate that the amount of Desmopressin that may be transferred to the child are considerably less than the amounts required to influence diuresis.

None.

A few per cent of treated patients can be expected to experience side effects such as fatigue, headache, nausea and abdominal pain.

Common (>1/100)

General: Headache, at high doses fatigue.

Circulation: at high doses: transient fall in blood pressure with a reflex tachycardia and facial flushing at the time of administration.

Gastro Intestinal: Abdominal pain, nausea.

Rare (<1/1000)

General: at high doses: dizziness.

Very rare (<1/10,000)

Metabolism: Hyponatraemia

Treatment without concomitant reduction of fluid intake may lead to fluid retention/hyponatraemia with or without accompanying signs and symptoms (headache, nausea/vomiting, weight gain, decreased serum sodium and in serious cases, convulsions).

Post marketing experience:

Isolated cases of allergic skin reactions and more severe general allergic reactions have been reported.

Overdose of OCTOSTIM solution can lead to fluid retention and hyponatraemia.

Treatment:

Although the treatment of hyponatraemia should be individualised, the following general recommendations can be given: Discontinue the desmopressin treatment, restrict fluid intake and treat symptoms if needed.

Pharmacotherapeutic group: Vasopressin & analogues, ATC code: H01B A02.

OCTOSTIM injection contains desmopressin, a structural analogue of the natural pituitary hormone arginine vasopressin. The difference lies in the desamination of cysteine and substitution of L-arginine by D-arginine. This results in a considerably longer duration of action and a complete lack of pressor effect in the dosages clinically used.

Desmopressin at high dosage, 0.3 micrograms/kg body weight intravenously, leads to a two- to fourfold increase in plasma of factor VIII coagulant activity (VIII:C). Also the content of von Willebrand factor-antigen (vWF:Ag) increases, but to a lesser extent. At the same time there is a release of plasminogen activator (tPA).

Administration of desmopressin has also been shown to lead to a shortening or normalisation of the bleeding time in patients with prolonged bleeding time as in uremia, liver cirrhosis, congenital or drug induced thrombocyte dysfunction and in patients with prolonged bleeding time of unknown etiology.

By administration of desmopressin instead of factor VIII concentrates the risk of transmission of HIV infection and hepatitis virus is avoided.

Plasma half life varies between 3-4 hours. The duration of the haemostatic effect depends on the half-life for VIII:C which is about 8-12 hours. The bioavailability following subcutaneous injection compared with intravenous administration is about 85%. Maximum plasma concentration after 0.3 micrograms/kg is achieved after approximately 60 minutes and it amounts to 600 pg/ml on average.

There were no unusual findings during the examination of the safety profile of desmopressin.

Sodium chloride

Hydrochloric acid (forpH adjustment)

Water for injections

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

4 years

OCTOSTIM solution for injection should be stored at 2° C - 8° C.

Colourless, Type I glass ampoule. One ampoule contains 1 ml solution.

Pack sizes: 10 x 1 ml.

For single use only. Discard any unused contents.

Ferring Ireland Ltd.

United Drug House

Magna Drive

Magna Business Park

Citywest Road

Dublin 24

PA 1009/14/1

Date of first authorisation: 28 April 2006

Date of last renewals: 28 April 2011

May 2015