Clinical Efficacy of Dacepton®

In contrast to levodopa, the therapeutic efficacy of apomorphine in Parkinson's disease (PD) is executed through direct stimulation of striatal postsynaptic dopamine receptors. It is independent of the presynaptic dopaminergic terminals for storage and release.1 Although the precise mechanism of action of apomorphine is not known, it is assumed to involve stimulation of the postsynaptic D1 and D2 receptors within the striatum (i.e. caudate nucleus and putamen).2

The clinical response to apomorphine correlates well with levels of apomorphine in the cerebrospinal fluid; the active substance distribution being best described by a two-compartment model. Apomorphine is rapidly and completely absorbed from subcutaneous tissue. When administered via the D-mine® Pen it has a rapid onset action (4-12 minutes), and the effect lasts for about 1 hour.  Its rapid clearance is explained by its short elimination half-life of around 33 minutes. The metabolism of apomorphine is by glucuronidation and sulphonation to at least ten per cent of the total; other pathways have not been described.3
The variation in absorption of apomorphine after subcutaneous injection can differ between individuals, but remains low within individual patients. Hence the lowest effective dose can differ significantly between patients therefore the doses have to be titrated individually.4

Safety of Dacepton®

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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.

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

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.

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.

1 Hagell P, Odin P: Apormorphine in the Treatment of Parkinson's Disease. Journal of Neuroscience Nursing 2001.
2 LeWitt PA: Subcutaneously administered apomorphine: pharmacokinetics and metabolism. Neurology 2004.
3 SmPC Dacepton® 5mg/ml Vial Solution for infusion, SmPC Dacepton® 10mg/ml Cartridge Solution for injection, in current version
4 Gancher ST, Woodward WR, Boucher B, Nutt JG: Peripheral pharmacokinetics of apomorphine in humans. Ann Neurol 1989.

5.  SmPC Dacepton®® 5mg/ml Vial solution for infusion (https://www.medicines.org.uk/emc/product/9632/smpc#gref), SmPC Dacepton®® 10mg/ml Cartridge solution for injection (https://www.medicines.org.uk/emc/product/9650/smpc#gref)