DACEPTON Solution for infusion Ref.[27682] Active ingredients: Apomorphine

Selection of Patients suitable for Dacepton 5 mg/ml solution for infusion

Patients selected for treatment with Dacepton 5 mg/ml solution for infusion 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 treatment with Dacepton 5 mg/ml solution for infusion.

Adults

Method of administration

Dacepton 5 mg/ml solution for infusion is a pre-diluted vial intended for use without dilution for subcutaneous use and to be administered as a continuous subcutaneous infusion by minipump and/or syringe-driver (see section 6.6). It is not intended to be used for intermittent 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 to slightly yellow and particle free solution should be used.

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.

Determination of Threshold Dose

The threshold dose for continuous infusion should be determined as follows: Continuous infusion is started at a rate of 1 mg apomorphine hydrochloride hemihydrate (0.2 ml) per hour then increased according to the individual response each day. Increases in the infusion rate should not exceed 0.5 mg at intervals of not less than 4 hours. Hourly infusion rates may range between 1 mg and 4 mg (0.2 ml and 0.8 ml), equivalent to 0.014-0.06 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 hemihydrate varies between individuals but, once established, remains relatively constant for each patient.

Precautions on continuing treatment

The daily dose of Dacepton 5 mg/ml solution for infusion varies widely between patients, typically within the range of 3-30 mg.

It is recommended that the total daily dose of apomorphine hydrochloride hemihydrate 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.

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

Dacepton 5 mg/ml solution for infusion is contraindicated 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 apomorphine. The management of elderly patients treated with apomorphine 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).

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.

Unopened: 30 months.

After opening and filling the drug product in syringes attached with infusion sets: chemical and physical in-use stability has been demonstrated for 7 days at 25°C. From a microbiological point of view, unless the method of opening and further handling precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

Single use only.

Discard any unused contents.

Keep the vials in the outer carton in order to protect from light.

Do not refrigerate or freeze.

For storage conditions after first opening of the medicinal product, see section 6.3.

Clear glass vials, type I with bromobutyl rubber stopper and a flip-off cap, containing 20 ml solution for infusion, in packs of 1, 5 or 30 vials.

Bundle packs: 5 × 1, 10 × 1, 30 × 1, 2 × 5 and 6 × 5.

Not all pack sizes may be marketed.

Do not use if the solution has turned green.

The solution should be inspected visually prior to use. Only clear and colourless to slightly yellow solutions without particles in undamaged containers should be used.

For single use only. Any unused medicinal product or waste material should be disposed in accordance with local requirements.

Continuous infusion and the use of a minipump and or syringe-driver

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.