APOMINE

What it is

APOMINE is a solution for injection in cartridge containing apomorphine hydrochloride hemihydrate 100 mg in 20 mL . It is a clear, colourless to slightly yellow sterile solution, practically free from visible particles . The product contains sulfites . Apomorphine is a directly acting dopamine receptor agonist, structurally related to dopamine, with high in vitro binding affinity for the dopamine D4 and D5 receptor . The effect of apomorphine as an antiparkinsonian agent is believed to be the result of direct stimulation of postsynaptic D2 dopamine receptors, but stimulation of presynaptic D2 dopamine receptors and antagonism of α2 adrenergic receptors may also be important .

Approved indications

— Reduce the number and severity of 'off' phases in patients with Parkinson's disease severely disabled by motor fluctuations refractory to conventional therapy .

Dosing overview

The optimal dosage of APOMINE must be determined on an individual patient basis . Hospital admission under appropriate specialist supervision is advised when establishing a patient's therapeutic regimen . Infusion rates can be commenced at 1 mg/hr, and then increased as necessary, with the maximum daily dose generally not exceeding 200 mg/day, and in clinical studies the required infusion rate varying between 1.25 and 5.5 mg/hr, with most patients requiring between 2 and 4 mg/hr . Infusions should be run for waking hours only, and unless the patient is experiencing night-time problems, 24 hour infusions are not advised .

Key safety warnings

It is essential that the patient is established on the antiemetic domperidone for at least 48–72 hours prior to initiation of therapy . Since apomorphine 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 apomorphine, especially at high doses, may have the potential for QT prolongation, caution should be exercised when treating patients at risk for Torsades de pointes arrhythmia, and when used in combination with domperidone, risk factors in the individual patient should be carefully assessed before treatment initiation and during treatment, including serious underlying heart conditions such as congestive cardiac failure, severe hepatic impairment or significant electrolyte disturbance, and monitoring for an effect on the QTc interval is advisable . Itchy nodular lesions at the injection site may be severe in patients on continuous subcutaneous infusions, with most patients experiencing injection site reactions particularly with continuous use, which may include subcutaneous nodules, induration, erythema, tenderness and panniculitis, and various other local reactions such as irritation, itching, bruising, fibrosis and pain may also occur . Apomorphine has been associated with somnolence, and patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with apomorphine .

Contraindications

APOMINE is contraindicated in patients with a known hypersensitivity or allergy to apomorphine, morphine or chemically related products . APOMINE should not be administered to patients with pre-existing neuropsychiatric problems or dementias due to either pathological processes, e.g. Alzheimer's disease, or to patients whose 'on' response to L-dopa is marred by severe dyskinesia, hypotonia or psychotoxicity . APOMINE is also contraindicated in patients with inadequate renal or liver function, unstable coronary vascular disease, cerebrovascular disease, respiratory depression or CNS depression . Concomitant use with 5HT3 antagonists including antiemetics (for example ondansetron, granisetron, palonosetron) is contraindicated . APOMINE is contraindicated for children and adolescents under 18 years of age . APOMINE is contraindicated in patients with a known hypersensitivity to sodium metabisulfite .

PBS listing

APOMINE injection containing apomorphine hydrochloride hemihydrate 100 mg in 20 mL is listed on the PBS with 4 items, streamlined restriction, at an ex-manufacturer price of A$412.63 .

Regulatory history

APOMINE apomorphine hydrochloride hemihydrate 100 mg/20 mL solution for infusion vial was first listed on the Australian Register of Therapeutic Goods on 2016-08-16 .