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Safety & Adverse Events

Reporting an adverse event

Please always consult the Summary of Product Characteristics (SmPC) before initiating treatment:

APO-go® PEN SmPC
APO-go® INFUSION SmPC

UK healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme: https://yellowcard.mhra.gov.uk/.2,3

Suspected adverse reactions should also be reported to the Britannia Pharmaceuticals Medical Information team.
Tel: +44 (0)1483 920 763 or [email protected].

What is Apomorphine?

The active component of the APO-go® PEN and the APO-go® INFUSION devices is apomorphine hydrochloride. Apomorphine is a direct stimulant of dopamine receptors, and has D1 and D2 receptor agonist properties.2,3 It was licensed in the UK in 1993 for use in patients whose disease was not adequately controlled with oral medication, and has since been used in clinical practice in many countries.12 

Although derived from morphine, apomorphine has no opiate or direct pain-killing properties and is not a controlled drug. APO-go is not a narcotic and is not addictive.

APO-go® is indicated for the treatment of motor fluctuations ('ON-OFF' phenomena) in patients with Parkinson's disease that are not sufficiently controlled by oral anti-Parkinson medication.

Common side effects2,3

Neuropsychiatric disturbances (including transient mild confusion and hallucinations) have occurred during apomorphine therapy. Transient sedation with each apomorphine dose may occur at the start of therapy; this usually resolves over the first few weeks.

Apomorphine has been associated with somnolence. Dizziness, light-headedness and yawning have also been reported.

Gastrointestinal side-effects include nausea and vomiting, particularly when apomorphine treatment is first initiated. This is usually as a result of the omission of the anti-emetic, domperidone, prior to treatment.

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. These can sometimes be reduced by rotating injection sites or using ultrasound to avoid problematic areas.

Contraindications2,3

APO-go® is contraindicated for children and adolescents under 18 years of age, and for patients with respiratory depression, dementia, psychotic diseases or hepatic insufficiency. It must not be administered to patients who have an 'ON' response to levodopa that is marred by severe dyskinesia or dystonia.

Hypersensitivity to the active substance or to any of the excipients is also a contraindication; it should not be administered to patients who have a known hypersensitivity to apomorphine or any excipients of the medicinal product.
 

Special warnings and precautions for use2,3

APO-go® 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 APO-go® 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 anti-hypertensives, and especially in patients with pre-existing postural hypotension.

Since APO-go®, 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 and 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.

APO-go® 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 to 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 APO-go®.

Caution is advised when combining APO-go® 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 APO-go®. Special care should be exercised when apomorphine is used in these patients.

APO-go® 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 whilst driving or operating machines during treatment with APO-go®. 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 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 APO-go®. 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 APO-go®. Before initiation of treatment, patients and caregivers should be warned of the potential risk of developing DDS.

APO-go® Pen 10 mg/ml Solution for Injection contains sodium bisulphite which may rarely cause severe allergic reactions and bronchospasm.

This medicinal product contains less than 1 mmol sodium (23 mg) per 10 ml, i.e. essentially “sodium-free”.
 

  1. 1. Parkinson’s and You. A guide for people new to the condition. https://www.parkinsons.org.uk/sites/default/files/2018-09/B181%20Parkinson%27s%20and%20you%20WEB.pdf. Accessed 20 Nov 2020.
  2. SmPC: APO-go Pen 10mg/ml Solution for Injection. https://www.medicines.org.uk/emc/product/2232/smpc. Accessed 20 Nov 2020.
  3. 3. SmPC: APO-go PFS 5mg/ml Solution for Infusion in Pre-filled Syringe. https://www.medicines.org.uk/emc/product/3908/smpc. Accessed 20 Nov 2020.
  4. 4. Antonini A & Jenner P. Apomorphine infusion in advanced Parkinson disease. Nat Rev Neurol. 2018;14:693-94.
  5. 5. Pfeiffer RF. Gastrointestinal dysfunction in Parkinson’s disease. Lancet Neurology 2003;2:107–16
  6. 6. Fasano A, Visanji NP, Liu LWC, et al. Gastrointestinal dysfunction in Parkinson’s disease. Lancet Neurol. 2015;14:625-39.
  7. 7. Stocchi F. The levodopa wearing-off phenomenon in Parkinson’s disease: pharmacokinetic considerations. Exp Opin Pharmacother 2006;7:1399-407.
  8. 8. Chapuis S, Ouchchane L, Metz O, et al. Impact of the motor complications of Parkinson’s disease on the quality of life. Mov Disord. 2005;20:224-30.
  9. 9. Trenkwalder C, Chaudhuri KR, García Ruiz PJ, et al. on behalf of an Expert Consensus Group for the use of apomorphine in Parkinson's disease. Expert Consensus Group report on the use of apomorphine in the treatment of Parkinson's disease - clinical practice recommendations. Parkinsonism Rel Disord 2015;21:1023-30.
  10. 10. Dewey RB Jr, Hutton JT, LeWitt PA, Factor SA. A randomized, double-blind, placebo-controlled trial of subcutaneously injected apomorphine for parkinsonian off-state events. Arch Neurol. 2001;58:1385-92.
  11. 11. Pfeiffer RF, Gutmannb L, Hull KL Jr, et al., the APO302 Study Investigators. Continued efficacy and safety of subcutaneous apomorphine in patients with advanced Parkinson’s disease. Parkinsonism Rel Disord 2007;13:93–100.
  12. 12. Katzenschlager R, Poewe W, Rascol O, et al. Apomorphine subcutaneous infusion in patients with Parkinson’s disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial. Lancet Neurol 2018;17:749-59.
  13. 13. Silverdale M. Continuous dopaminergic stimulation in Parkinson’s disease. Prog Neurol Psychiatr 2007;11:24-8.
  14. 14. Pietz K, Hagell P, Odin P. J Neurol Neurosurg Psychiatry 1998;65:709–716.
  15. 15. Kanovsky P, et al. Mov Disord 2002;17(1):188–191.

Close

AM IMPAKT Study interim results. Presented at International Parkinson and Movement Disorder Society. Treatment of Parkinson’s Disease: Past, Present and Future. March 2014, Miami, Florida, USA.
Antonini A, et al. Parkinsonism and Relat Disord 2009;15S:S97-S100.
APO-go PEN SmPC
APO-go PFS SmPC
Chaudhuri KR, Ondo W. Handbook of Movement Disorders, Current Medicine Group, 2009.
Deleu D, Hanssens Y, Northway MG. Drugs and Aging 2004;21(11):687–709.
Dewey et al. Arch.Neurol 2001;58(9):1385–92.
Drapier S, et al.Parkinsonism and Relat Disord 2012;18:40-44.
Hagell P, Odin P. J Neurosci Nurs 2001;33(1):21–38.
NICE Guidelines for Parkinson’s Disease: National clinical guidelines for diagnosis and management in primary and secondary care. Royal College of Physicians, published June 2006.
Pietz K, Hagell P, Odin P. J Neurol Neurosurg Psychiatry 1998;65(5):709–16.
Riederer P et al. Parkinsonism Relat Disord 2007;13(8):466–79.
Rizos A, et al. Poster presented at MDPD, Seoul, 2013.
Ruiz PJG, et al. Movement Disord 2008;23(8):1130-1136.
Silverdale M. Continuous dopaminergic stimulation in Parkinson’s disease. Progress in Neurology and Psychiatry .2007;11(1):24-28.
Stacy M. J Neural Transm 2010;117:837-846.
Stocchi F. Neurol Sci 2008;29:S383-S386.
Todd A, James C-A. Apomorphine nodules in Parkinson’s disease: Best Practice management. British Journal of Community Nursing, Clinical Review 2008;13(10):457-63.
Bhidayasiri R, Chaudhuri K R, LeWitt P, et al. Clin Neuropharm 2015;38:89–103.

Parkinson’s UK Website. https://www.parkinsons.org.uk/content/parkinsons-symptoms.

Prescribing Information Report an adverse event References