An evaluation of subcutaneous apomorphine for the treatment of Parkinson’s disease

ABSTRACT

Introduction

Heterogeneity of symptoms and individual variability of progression characterizes Parkinson’s disease. Unmet therapeutic needs include a cure, disease modification, and improvement of available marketed dopamine-substituting compounds. Personalized treatment, tailored to the patients’ needs and symptoms, aims to ameliorate impaired motor behavior and non-motor features. Injection or infusion of apomorphine is a therapeutic option for more advanced patients with severe levodopa associated motor complications.

Areas covered

This narrative review summarizes the subcutaneous administration, efficacy, and side effects of the non-ergot derivative dopamine agonist apomorphine following a non-systematic literature research.

Expert opinion

Subcutaneous apomorphine hydrochloride application rapidly terminates intervals with severe motor impairment with bolus injections. Oscillation of motor behavior well responds to continuous apomorphine infusions. Long-term application of the commercially available apomorphine hydrochloride solution sooner or later affects skin and oral mucosa. Onset of skin nodules associated with subcutaneous tissue inflammation probably results from the antioxidant preservative sodium metabisulfite in the apomorphine solution. Addition of another better tolerated and safer antioxidant instead of sodium metabisulphite or use of an already available concentrated apomorphine-free base formulation will enhance its future use, its tolerability, safety, and acceptance of subcutaneous and sublingual application.

KEYWORDS:

• Apomorphine
• Parkinson’s disease
• subcutaneous
• motor complications

Article highlights

• Apomorphine is an old non ergot dopamine agonist, which shares pharmacological properties of dopamine.

• Subcutaneous apomorphine delivery via a pump system is employed for amelioration of motor complications in patients with Parkinson’s disease .

• Subcutaneous apomorphine bolus injections quickly terminate OFF periods in patients with Parkinson’s disease.

• The antioxidant sodium metabisulphite in the apomorphine solution is probably responsible for onset of skin irritability and inflammatory skin lesions during long term apomorphine use.

• The future use of the current available apomorphine hydrochloride solution is more uncertain than ever due to the availability of better tolerable and safe drug treatment alternatives.

Declaration of interest

TH Muller declares that between 2012 and 2013, he received honoraria for advisory board participation and for talks on apomorphine from Archimedes Pharm. Furthermore, in 2015, he participated in a workshop on apomorphine pump therapy sponsored by Desitin in his department. In 2018/2019, he received honoraria for two advisory board meetings from STADA Pharma on the application of apomorphine pump. Furthermore, in 2018/2019, he participated in a workshop on Parkinson’s disease sponsored by Desitin (who market PD drug piribedil and the apomorphine pump system in Germany), BIAL (who market PD drug opicapone), Zambon (who market PD drug safinamide), and AbbVie (who market PD drug Duodopa) courtesy of an unrestricted educational grant. He has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One referee declares that he gave speeches in 2019 and 2019 for Zambon related to Parkinson’s disease therapy. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript was not funded.