General Information

Apokyn (apomorphine) is a non-ergoline dopamine agonist. Formulations of apomorphine have been available since the 1970s in Europe and Canada, but Apokyn represents the first time any drug containing apomorphine has been approved for use in the US. It is indicated for the treatment of motor symptoms associated with late stage Parkinson's Disease.

It is specifically indicated 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, as adjunct/supplemental therapy to standard levodopa therapy. It is the first treatment approved for this indication in the US.

The recommended subcutaneous dose of Apokyn is 0.2 to 0.6 mL subcutaneously during acute hypomobility episodes, delivered via metered injector pen. Average dosing frequency during study was thrice daily, with a maximum studied regimen of 0.6 mL five times daily. Recommended application is to a pinch of skin on the upper arm, thigh or abdomen.

Clinical Results

FDA approval of Apokyn for the treatment of acute Parkinsonian hypomobility was based on three randomized, controlled studies, enrolling a total of 108 subjects, all of whom had advanced Parkinson's disease (mean disease duration = 11.3 years) and were being treated with L-dopa and at least one other agent, usually a dopamine agonist. Improvement in motor function on the Unified Parkinson’s Disease Rating Scale (UPDRS) was the primary endpoint of all three studies. The trials enrolled a combined total of 108 subjects, including 29 (one trial) who had never received apomorphine products (the remaining 79 subjects had experience internationally with apomorphine). Results showed that Apokyn was significantly efficacious in ending hypomotor episodes and markedly impoving UPDRS motor scores (> 20 points mean improvement for all trials) 20 minutes after dosing, compared with placebo (p<0.0001 for all trials). 98% of all trial subjects began antiemetic treatment with Tigan (trimethobenzamide) 3 days prior to treatment; roughly 50% were able to eventually disontinue Tigan while continuing Apokyn treatment (mean time to discontinuation = 2 months).

Side Effects

Adverse events associated with the use of Apokyn may include (but are not limited to) the following:

Yawning

Dyskinesias

Drowsiness/Somnolence

Dizziness/Postural Hypotension

Rhinorrhea

Hallucinations

Edema/Inflammation

In addition, Apokyn has been associated with a very high incidence on mild-to-moderate treatment-responsive nausea and/or vomiting, especially early in treatment while the subject is still acclimating to Apokyn. It is recommended that subjects begin antiemetic treatment with or just prior to treatment with Apokyn, and continue for as long as needed.

Mechanism of Action

Apokyn injection delivers apomorphine hydrochloride hemihydrate, a non-ergoline dopamine agonist with high selectivity for the dopamine D4, D2, D3, D5 and adrenergic alpha-1D, alpha-2B, alpha-2C receptors, all of which are broadly associated with the promotion of motor function. The precise mechanism of action of Apokyn as a treatment for Parkinson's disease is unknown, although it is believed to be due to stimulation of post-synaptic D2 receptors within the caudate putamen, a brain stucture which supports motor function. Subcutaneous administration provides rapid, controlled systemic delivery, with linear pharmacokinetics over a doses ranging of 2 to 8 mg.

Literature References

Bowron A. Practical considerations in the use of apomorphine injectable. Neurology. 2004 Mar 23;62(6 Suppl 4):S32-6.

Di Rosa AE, Epifanio A, Antonini A, Stocchi F, Martino G, Di Blasi L, Tetto A, Basile G, Imbesi D, La Spina P, Di Raimondo G, Morgante L. Continuous apomorphine infusion and neuropsychiatric disorders: a controlled study in patients with advanced Parkinson's disease. Neurological Sciences 2003 Oct;24(3):174-5.

Stocchi F, Berardelli A, Vacca L, Barbato L, Monge A, Nordera G, Ruggieri S. Apomorphine infusion and the long-duration response to levodopa in advanced Parkinson's disease. Clinical Neuropharmacology 2003 May-Jun;26(3):151-5.