Overview
11 DESCRIPTION apomorphine hydrocloride (apomorphine hydrochloride injection) contains apomorphine hydrochloride, a non-ergoline dopamine agonist. Apomorphine hydrochloride is chemically designated as 6aβ-Aporphine-10,11-diol hydrochloride hemihydrate with a molecular formula of C 17 H 17 NO 2 ∙ HCl ∙ ½ H 2 O.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Apomorphine hydrocloride is a non-ergoline dopamine agonist with high in vitro binding affinity for the dopamine D 4 receptor, and moderate affinity for the dopamine D 2 , D 3 , and D 5 , and adrenergic α 1 D, α 2 B, α 2 C receptors. The precise mechanism of action of apomorphine hydrocloride as a treatment for Parkinson's disease is unknown, although it is believed to be due to stimulation of post-synaptic dopamine D 2 -type receptors within the caudate-putamen in the brain. 12.2 Pharmacodynamics Prolongation of the QTc Interval In a thorough QT study at exposures similar to those achieved with the recommended dosing, apomorphine resulted in a prolongation of QTcF of 10 msec (90% upper confidence interval of 16 msec).
Indications
- 1 INDICATIONS AND USAGE Apomorphine hydrochloride injection is indicated for the acute, intermittent treatment of hypomobility, "off" episodes ("end-of-dose wearing off" and unpredictable "on/off" episodes) in patients with advanced Parkinson's disease. Apomorphine hydrocloride inejction has been studied as an adjunct to other medications [see Clinical Studies (14) ] . Apomorphine hydrocloride injection is a non-ergoline dopamine agonist indicated for the acute, intermittent treatment of hypomobility, "off" episodes ("end-of-dose wearing off" and unpredictable "on/off" episodes) associated...
Common Doses
- 0.2 mL
- 2 mg
- 0.6 mL
- 0.1 mL
Dosage
2 DOSAGE AND ADMINISTRATION For subcutaneous use only ( 2.1 ) Always express apomorphine hydrocloride dose in mL to minimize dosing errors ( 2.1 ) The starting dose of apomorphine hydrocloride is 0.2 mL (2 mg); give the first dose under medical supervision; titrate the dose to effect and tolerance; the maximum recommended dose is 0.6 mL ( 2.3 ) Treatment with a concomitant antiemetic, e.g., trimethobenzamide, is recommended, starting 3 days prior to the first dose of apomorphine hydrocloride.
Contraindications
- 4 CONTRAINDICATIONS Apomorphine hydrocloride is contraindicated in patients: Using concomitant drugs of the 5HT 3 antagonist class including antiemetics (e.g., ondansetron, granisetron, dolasetron, palonosetron) and alosetron [see Drug Interactions (7.1) ] . There have been reports of profound hypotension and loss of consciousness when apomorphine hydrocloride was administered with ondansetron. With hypersensitivity/allergic reaction to apomorphine or to any of the excipients of apomorphine hydrocloride, including a sulfite (i.e., sodium metabisulfite).
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are discussed in more detail in the Warnings and Precautions section of labeling: Serious Adverse Reactions After Intravenous Administration [see Warnings and Precautions (5.1) ] Nausea and Vomiting [see Warnings and Precautions (5.2) ] Falling Asleep During Activities of Daily Living and Somnolence [see Warnings and Precautions (5.3) ] Syncope/Hypotension/Orthostatic Hypotension [see Warnings and Precautions (5.4) ] Falls [see Warnings and Precautions (5.5) ] Hallucinations/Psychotic-Like Behavior [see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS Concomitant use of antihypertensive medications and vasodilators: increased risk for hypotension, myocardial infarction, pneumonia, falls, and injuries ( 7.2 ) Dopamine antagonists such as neuroleptics or metoclopramide, may diminish the effectiveness of apomorphine hydrocloride ( 7.4 ) 7.1 5HT 3 Antagonists Based on reports of profound hypotension and loss of consciousness when apomorphine hydrocloride was administered with ondansetron, the concomitant use of apomorphine hydrocloride with 5HT 3 antagonists including antiemetics (for example, ondansetron, granisetron,...