APO-GO Solution for injection Ref.[6203] Active ingredients: Apomorphine

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. Before the decision to initiate domperidone and apomorphine treatment, risk factors for QT interval prolongation in the individual patient should be carefully assessed to ensure that the benefit outweighs the risk (see section 4.4).

Apomorphine should be initiated in the controlled environment of a specialist clinic. The patient should be supervised by a physician experienced in the treatment of Parkinson’s disease (e.g. neurologist). The patient’s treatment with levodopa, with or without dopamine agonists, should be optimised before starting APO-go treatment.

Posology

Determination of the threshold dose

The appropriate dose for each patient is established by incremental dosing schedules.

The following schedule is suggested:

1 mg of apomorphine HCl (0.1 ml), that is approximately 15-20 micrograms/kg, may be injected subcutaneously during a hypokinetic, or ‘off’ period and the patient is observed over 30 minutes for a motor response.

If no response, or an inadequate response, is obtained a second dose of 2 mg of apomorphine HCl (0.2 ml) is injected subcutaneously and the patient observed for an adequate response for a further 30 minutes.

The dosage may be increased by incremental injections with at least a forty minute interval between succeeding injections, until a satisfactory motor response is obtained.

Establishment of treatment

Once the appropriate dose is determined a single subcutaneous injection may be given into the lower abdomen or outer thigh at the first signs of an ‘off’ episode. It cannot be excluded that absorption may differ with different injection sites within a single individual. Accordingly, the patient should then be observed for the next hour to assess the quality of their response to 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, given as 1-10 injections and sometimes as many as 12 separate injections per day.

It is recommended that the total daily dose of apomorphine HCl should not exceed 100mg and that individual bolus injections should not exceed 10 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.

Once treatment has been established domperidone therapy may be gradually reduced in some patients but successfully eliminated only in a few, without any vomiting or hypotension.

Paediatric population

APO-go Pen 10 mg/ml Solution for Injection is contra-indicated for children and adolescents under 18 years of age (see section 4.3).

Elderly

The elderly are well represented in the population of patients with Parkinson’s disease and constitute a high proportion of those studied in clinical trials of APO-go. The management of elderly patients treated with APO-go has not differed from that of younger patients. However, extra caution is recommended during initiation of therapy in elderly patients because of the risk of postural hypotension.

Renal impairment

A dose schedule similar to that recommended for adults, and the elderly, can be followed for patients with renal impairment (see section 4.4).

Method of Administration

APO-go Pen 10 mg/ml Solution for Injection is for subcutaneous use by intermittent bolus injection.

<Apomorphine must not be used via the intravenous route.

Do not use if the solution has turned green. The solution should be inspected visually prior to use. Only clear, colourless and particle free solution should be used.

There is little clinical experience of overdose with apomorphine by this route of administration. Symptoms of overdose may be treated empirically as suggested below:

• excessive emesis may be treated with domperidone.
• respiratory depression may be treated with naloxone.
• hypotension: appropriate measures should be taken, e.g. raising the foot of the bed.
• bradycardia may be treated with atropine.

2 years.

48 hours after first opening.

Do not store above 25°C.

Keep the container in the outer carton to protect from light.

The product should be stored at the same conditions after opening and between withdrawals.

Cartridge.

APO-go Pen 10 mg/ml is a disposable multiple dose pen injector system incorporating a clear glass (type I) cartridge containing a clear solution for injection. The glass cartridge is sealed at one end with a bromobutyl rubber piston, and at the other end with a bromobutyl rubber/aluminium membrane.

Each pen contains 3 ml of solution for injection.

Packs containing 1, 5, or 10 × 3 ml pens in a moulded plastic tray in an outer cardboard carton.

Multipacks containing 25 (5 packs of 5) pens.

Not all pack sizes may be marketed.

APO-go PEN

Do not use if solution has turned green.

Discard each pen no later than 48 hours from first use.

(see attached diagram)

* This pack does NOT contain needles for use with your Pen.

Use pen needles not more than 12 mm (½") in length and not finer than 0.33 mm (29G). Pen needles recommended for use with insulin pens are compatible with APO-go Pen.

IMPORTANT: Do not pull the red capped dial (see 1) before you have set the dosage (see ‘Selecting the correct dosage’).

Attaching the needle:

a Before using APO-go Pen you will need some surgical wipes and one needle in its protective cone (see 2).

b Take the Pen out of its box and remove the outer sleeve (see 3).

c Wipe the membrane of the Pen (see 4) with a surgical wipe.

d Peel off the paper from the needle cone (see 2).

e It is important to bring the needle to the Pen in a straight line, as shown above. If the needle is presented at an angle it may cause the Pen to leak.

f Screw the cone (see 2) clockwise onto the membrane until it is tight. This securely attaches the needle.

g Remove the protective cone (see 5), but do not throw it away. Do not remove the needle protector (see 6) at this stage.

h Replace the Pen’s outer sleeve (see 3).

Selecting the correct dose

i Press the red capped dosage dial (see 1) and whilst holding it down, turn the dial clockwise until the arrow points to the dose your doctor chose for you (see 7&8). Release the downward pressure on the red capped dial. The dose is now set and you do not need to redial for subsequent injections.

Important: If you pass your prescribed dose while turning the dial, just continue pressing and turning in the same direction until the arrow points to the dose your doctor chose for you.

Never pull and turn the red capped dosage dial at the same time.

If your dose is 1 mg, start by emptying a 1 mg dose onto a paper tissue and discarding it. This is called ‘priming’ and is important because it ensures you get a full dose the first time you use your Pen. Then, set the dose you require for injection and inject it in the usual way (see “Injecting”). If the first dose required is more than 1 mg, you do not need to prime the Pen.

Injecting:

j Once you have set the dose, gently pull out the red capped dosage dial as far as it will go. Check the red scale on the plunger (see 9) and inject only if the line that is just visible matches the intended dose.

k Using a surgical wipe, clean the area of skin where you plan to inject the medicine and around it.

l Remove the Pen’s outer sleeve (see 3).

m Remove the needle protector (see 6).

n Insert the needle (see 10) into the skin as shown by your doctor.

o To inject, press the red capped dosage dial (see 1) down as far as it will go, using your thumb if possible. Once the red capped dosage dial is fully depressed, count to three before withdrawing the needle.

p Replace the protective cone (see 5) onto the used needle and push gently into place. Once secure, turn the needle anti-clockwise to unscrew it. Keep the needle in its protective cone and discard it in a safe place, such as a “Sharps” bin or an empty coffee jar.

Preparing for the next injection:

q Remove the outer sleeve of the Pen and check there is enough apomorphine left in the cartridge for your next injection. If there is, put a new needle in place in the same way as before.

r If there is not enough apomorphine left for another injection, prepare another pen.

s Finally, replace the outer sleeve of your Pen.