indication

For the acute, intermittent treatment of hypomobility, off episodes (end-of-dose wearing off and unpredictable on/off episodes) associated with advanced Parkinson's disease.

pharmacology

Apomorphine is a type of dopaminergic agonist, a morphine derivative which primarily affects the hypothalamic region of the brain. Drugs containing this substance are sometimes used in the treatment of Parkinson's disease or erectile dysfunction. In higher doses it is a highly effective emetic.

mechanism of action

The precise mechanism of action of apomorphine as a treatment for Parkinson's disease is unknown, although it is believed to be due to stimulation of post-synaptic dopamine D2-type receptors within the brain. Apomorphine has been shown to improve motor function in an animal model of Parkinson's disease. In particular, apomorphine attenuates the motor deficits induced by lesions in the ascending nigrostriatal dopaminergic pathway with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in primates.

toxicity

LD₅₀=0.6 mmoles/kg (mice, intraperitoneal)

biotransformation

Hepatic

absorption

100% following subcutaneous administration

half life

40 minutes (range 30 - 60 minutes)

drug interactions

Artemether: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Entacapone: Entacapone increases the effect and toxicity of the sympathomimetic, apomorphine.

Lumefantrine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Paliperidone: The atypical antipsychotic agent, paliperidone, may decrease the therapeutic effect of the anti-Parkinson's agent, apomorphine. This interaction may be due to the dopamine antagonist properties of paliperidone. Consider an alternate antipsychotic in those with Parkinson's disease or consider using clozapine or quetiapine if an atypical antipsychotic is necessary.

Tacrolimus: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Thiothixene: May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Thiothixene may also antagonize the effects of the anti-Parkinsonian agent, Apomorphine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or doses changed.

Toremifene: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.

Voriconazole: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Vorinostat: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Ziprasidone: Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Zuclopenthixol: Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). Antagonism may also occur between zuclopenthixol, a dopamine D2 receptor antagonist, and apomorphine, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.