Apomorphine

Apomorphine hydrochloride

Indications : Treatment of motor fluctuations (“on-off” phenomena) in patients with Parkinson’s disease which are not sufficiently controlled by oral anti-Parkinson medication

Dosage and Administration Apomorphine : hydrochloride is administered subcutaneously by continuous subcutaneous infusion. 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 startingtreatment. The appropriate dose for each patient is established by incremental dosing schedules. Continuous infusion is started at a rate of 1 mg apomorphine HCl (0.1 ml) per hour then increased according to the individual response. Increases in the infusion rate should not exceed 0.5 mg per hour at intervals of not less than 4 hours. Hourly infusion rates may range between 1 mg and 4 mg (0.1 ml and 0.4 ml), equivalent to 0.015 - 0.06 mg/kg/hour. Infusions should run for waking hours only. 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 should be carefully assessed individual bolus injections should not exceed 10mg and the total daily dose should not exceed 100mg. Only clear, colourless and particle free solution should be used. Apomorphine must not be used via the intravenous route.

Contraindications : Children and adolescents (up to 18 years of age). Known hypersensitivity to apomorphine or any excipients of the medicinal product. Respiratory depression, dementia, psychotic disease or hepatic insufficiency.

Pregnancy and lactation : Apomorphine should not be used in pregnancy unless clearly necessary. Breastfeeding: It is not known whether apomorphine is excreted in breast milk.

Ability to drive and operate machinery : Apomorphine has minor or moderate influence on the ability to drive and use machines. Patients being treated with apomorphine and presenting with somnolence and/or sudden sleep episodes must be informed to refrain from driving or engaging in activities (e.g. operating machines)

Interactions : There is potential for interaction with neuroleptic and antihypertensive agents and cardiac active medicinal products. It is recommended to avoid the administration of apomorphine with other drugs known to prolong the QT interval.

Precautions : Use with caution in patients with renal, pulmonary or cardiovascular disease, or who are prone to nausea or vomiting. Apomorphine may produce hypotension Neuropsychiatric disturbances may be exacerbated by apomorphine. Apomorphine has been associated with somnolence and episodes of sudden sleep onset. Haematology tests should be undertaken at regular intervals as haemolytic anaemia and thrombocytopenia have been reported. Dopamine dysregulation Syndrome (DDS) is an addictive disorder resulting in excessive use of the product seen in some patients. Apomorphine may have the potential for QT prolongation, exercised caution when treating patients at risk for torsades depointes arrhythmia. An ECG should be performed prior to treatment with domperidone. Patients should report possible cardiac symptoms. palpitations, syncope, or near-syncope and clinical changes that could lead to hypokalaemia, Apomorphine has been associated with local subcutaneous effects that can be sometimes reduced by rotation of injection sites in order to avoid nodularity and induration. Contains sodium metabisulphite which may rarely cause severe allergic reactions and bronchospasm.

Side Effects : Very common: Hallucinations and injection site reactions. Common: Neuropsychiatric disturbances, somnolence, transient sedation, dizziness, yawning, nausea and vomiting. Rarely, injection site necrosis and ulceration, Severe drug-induced dyskinesias, Postural hypotension, Positive Coombs’ tests, haemolytic anaemia, thrombocytopenia, Eosinophilia, impulse control disorders.Rarely, allergic reactions (including anaphylaxis and bronchospasm) due to sodium metabisulphite. Symptoms of overdose like excessive emesis, respiratory depression, hypotension and bradycardia