APO-GO PFS

Selection of Patients Suitable for APO-go injections:

Patients selected for treatment with APO-go should be able to recognise the onset of their ‘off’ symptoms and be capable of injecting themselves or else have a responsible carer able to inject for them when required. Patients treated with apomorphine will usually need to start domperidone at least two days prior to initiation of therapy.

The domperidone dose should be titrated to the lowest effective dose and discontinued as soon as possible. 4). Apomorphine should be initiated in the controlled environment of a specialist clinic. g. neurologist). The patient’s treatment with levodopa, with or without dopamine agonists, should be optimised before starting APO-go treatment.

Posology Continuous Infusion Patients who have shown a good ‘on’ period response during the initiation stage of apomorphine therapy, but whose overall control remains unsatisfactory using intermittent injections, or who require many and frequent injections (more than 10 per day), may be commenced on or transferred to continuous subcutaneous infusion by minipump and / or syringe driver as follows:- The choice, of which minipump and / or syringe-driver to use, and the dosage settings required, will be determined by the physician in accordance with the particular needs of the patient.

2 ml) per hour then increased according to the individual response each day. 5 mg at intervals of not less than 4 hours. 06 mg/kg/hour. Infusions should run for waking hours only. Unless the patient is experiencing severe night-time problems, 24 hour infusions are not advised.

Tolerance to the therapy does not seem to occur as long as there is an overnight period without treatment of at least 4 hours. In any event, the infusion site should be changed every 12 hours. Patients may need to supplement their continuous infusion with intermittent bolus boosts, as necessary, and as directed by their physician.

A reduction in dosage of other dopamine agonists may be considered during continuous infusion. Establishment of treatment. Alterations in dosage may be made according to the patient’s response. The optimal dosage of apomorphine hydrochloride varies between individuals but, once established, remains relatively constant for each patient.

Precautions on continuing treatment The daily dose of APO-go varies widely between patients, typically within the range of 3-30 mg. It is recommended that the total daily dose of apomorphine HCl should not exceed 100 mg. In clinical studies it has usually been possible to make some reduction in the dose of levodopa; this effect varies considerably between patients and needs to be carefully managed by an experienced physician.

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 HCl.

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 HCl therapy. 4). Aggression, agitation.

Nervous system disorders Common:

Transient sedation with each dose of apomorphine HCl 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. 4. 4).

Respiratory, thoracic and mediastinal disorders Common:

Yawning has been reported during apomorphine therapy.

Uncommon:

Apomorphine HCl 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 pretreatment, 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.

In patients with respiratory depression, dementia, psychotic diseases or hepatic insufficiency. Apomorphine HCl treatment must not be administered to patients who have an ‘on’ response to levodopa which is marred by severe dyskinesia or dystonia.

1. APO- go should not be administered to patients who have a hypersensitivity to apomorphine or any excipients of the medicinal product. 5). APO-go is contra-indicated for children and adolescents under 18 years of age.