DACEPTON Solution for infusion Ref.[27682] Active ingredients: Apomorphine

Apomorphine hydrochloride hemihydrate should be given with caution to patients with renal, pulmonary or cardiovascular disease and persons prone to nausea and vomiting.

Extra caution is recommended during initiation of therapy in elderly and/or debilitated patients.

Since apomorphine may produce hypotension, even when given with domperidone pre-treatment, care should be exercised in patients with pre-existing cardiac disease or in patients taking vasoactive medicinal products such as antihypertensives, and especially in patients with pre-existing postural hypotension.

Since apomorphine, especially at high dose, may have the potential for QT prolongation, caution should be exercised when treating patients at risk for torsades de pointes arrhythmia.

When used in combination with domperidone, risk factors in the individual patient should be carefully assessed. This should be done before treatment initiation, and during treatment. Important risk factors include serious underlying heart conditions such as congestive cardiac failure, severe hepatic impairment or significant electrolyte disturbance. Also medication possibly affecting electrolyte balance, CYP3A4 metabolism or QT interval should be assessed. Monitoring for an effect on the QTc interval is advisable. An ECG should be performed:

• prior to treatment with domperidone
• during the treatment initiation phase
• as clinically indicated thereafter

The patient should be instructed to report possible cardiac symptoms including palpitations, syncope, or near-syncope. They should also report clinical changes that could lead to hypokalaemia, such as gastroenteritis or the initiation of diuretic therapy.

At each medical visit, risk factors should be revisited.

Apomorphine is associated with local subcutaneous effects. These can sometimes be reduced by the rotation of injection sites or possibly by the use of ultrasound (if available) in order to avoid areas of nodularity and induration.

Haemolytic anaemia and thrombocytopenia have been reported in patients treated with apomorphine. Haematology tests should be undertaken at regular intervals as with levodopa, when given concomitantly with apomorphine.

Caution is advised when combining apomorphine with other medicinal products, especially those with a narrow therapeutic range (see Section 4.5).

Neuropsychiatric problems co-exist in many patients with advanced Parkinson’s disease. There is evidence that for some patients neuropsychiatric disturbances may be exacerbated by apomorphine. Special care should be exercised when apomorphine is used in these patients.

Apomorphine has been associated with somnolence, and episodes of sudden sleep onset, particularly in patients with Parkinson’s disease. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with apomorphine. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines. Furthermore, a reduction of dosage or termination of therapy may be considered.

Impulse control disorders

Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including apomorphine. Dose reduction/tapered discontinuation should be considered if such symptoms develop.

Dopamine dysregulation Syndrome (DDS) is an addictive disorder resulting in excessive use of the product seen in some patients treated with apomorphine. Before initiation of treatment, patients and caregivers should be warned of the potential risk of developing DDS.

Dacepton 5 mg/ml solution for infusion contains sodium metabisulphite which may rarely cause severe hypersensitivity reactions and bronchospasm.

Dacepton 5 mg/ml contains 3.4 mg sodium per ml. To be taken into consideration by patients on a controlled sodium diet.

Patients selected for treatment with apomorphine hydrochloride hemihydrate are almost certain to be taking concomitant medications for their Parkinson’s disease. In the initial stages of apomorphine hydrochloride hemihydrate therapy, the patient should be monitored for unusual side-effects or signs of potentiation of effect.

Neuroleptic medicinal products may have an antagonistic effect if used with apomorphine. There is a potential interaction between clozapine and apomorphine, however clozapine may also be used to reduce the symptoms of neuropsychiatric complications.

If neuroleptic medicinal products have to be used in patients with Parkinson’s disease treated by dopamine agonists, a gradual reduction in apomorphine dose may be considered when administration is by minipump and or syringe-driver (symptoms suggestive of neuroleptic malignant syndrome have been reported rarely with abrupt withdrawal of dopaminergic therapy).

The possible effects of apomorphine on the plasma concentrations of other medicinal products have not been studied. Therefore caution is advised when combining apomorphine with other medicinal products, especially those with a narrow therapeutic range.

Antihypertensive and Cardiac Active Medicinal Products

Even when co-administered with domperidone, apomorphine may potentiate the antihypertensive effects of these medicinal products (see Section 4.4).

It is recommended to avoid the administration of apomorphine with other drugs known to prolong the QT interval.

Pregnancy

There is no experience of apomorphine usage in pregnant women.

Animal reproduction studies do not indicate any teratogenic effects, but doses given to rats which are toxic to the mother can lead to failure to breathe in the newborn. The potential risk for humans is unknown. See Section 5.3.

Dacepton 5 mg/ml solution for infusion should not be used during pregnancy unless clearly necessary

Breast-feeding

It is not known whether apomorphine is excreted in breast milk. A decision on whether to continue/discontinue breastfeeding or to continue/discontinue therapy with Dacepton 5 mg/ml solution for infusion should be made taking into account the benefit of breast-feeding to the child and the benefit of Dacepton 5 mg/ml solution for infusion to the woman.

Apomorphine hydrochloride hemihydrate has minor or moderate influence on the ability to drive and use machines.

Patients being treated with apomorphine and presenting with somnolence and/or sudden sleep episodes must be informed to refrain from driving or engaging in activities (e.g. operating machines) where impaired alertness may put themselves or others at risk of serious injury or death until such recurrent episodes and somnolence have resolved (see also section 4.4).

Very common: (≥1/10), Common: (≥1/100 to <1/10), Uncommon: (≥1/1,000 to <1/100), Rare: (≥1/10,000 to <1/1,000), Very rare: (<1/10,000), Not known: (cannot be estimated from the available data)

Blood and lymphatic system disorders

Uncommon: Haemolytic anaemia and thrombocytopenia have been reported in patients treated with apomorphine.

Rare: Eosinophilia has rarely occurred during treatment with apomorphine hydrochloride hemihydrate.

Immune system disorders

Rare: Due to the presence of sodium metabisulphite, allergic reactions (including anaphylaxis and bronchospasm) may occur.

Psychiatric disorders

Very common: Hallucinations

Common: Neuropsychiatric disturbances (including transient mild confusion and visual hallucinations) have occurred during apomorphine hydrochloride hemihydrate therapy.

Not known:

Impulse control disorders:

Pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including apomorphine (see section 4.4).

Aggression, agitation.

Nervous system disorders

Common: Transient sedation with each dose of apomorphine hydrochloride hemihydrate at the start of therapy may occur; this usually resolves over the first few weeks. Apomorphine is associated with somnolence. Dizziness/light-headedness have also been reported.

Uncommon: Apomorphine may induce dyskinesias during “on” periods which can be severe in some cases, and in a few patients may result in cessation of therapy. Apomorphine has been associated with sudden sleep onset episodes. See section 4.4.

Unknown: Syncope

Vascular disorders

Uncommon: Postural hypotension is seen infrequently and is usually transient (see section 4.4)

Respiratory, thoracic and mediastinal disorders

Common: Yawning has been reported during apomorphine therapy

Uncommon: Breathing difficulties have been reported.

Gastrointestinal disorders

Common: Nausea and vomiting, particularly when apomorphine treatment is first initiated, usually as a result of the omission of domperidone (See section 4.2).

Skin and subcutaneous tissue disorders

Uncommon: Local and generalised rashes have been reported.

General disorders and administration site conditions

Very common: Most patients experience injection site reactions, particularly with continuous use. These may include subcutaneous nodules, induration, erythema, tenderness and panniculitis. Various other local reactions (such as irritation, itching, bruising and pain) may also occur.

Uncommon: Injection site necrosis and ulceration have been reported

Not Known: Peripheral oedema has been reported.

Investigations

Uncommon: Positive Coombs' tests have been reported for patients receiving apomorphine.

Reporting of suspected adverse reactions

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.

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