Usual Adult Dose for Parkinson's Disease

Dose initiation should be supervised by a healthcare provider: Antiemetic premedication should be initiated prior to therapy due to high incidence of nausea and vomiting

SUBLINGUAL ADMINISTRATION:

• Initial dose: 10 mg sublingually during an "off" episode; monitor blood pressure and pulse
• Titration: If initial dose is tolerated, but response is insufficient, increase in increments of 5 mg and assess response until an effective and tolerable dose is achieved; allow at least 2 hours between doses
• Maintenance Dose: 10 to 30 mg sublingually as needed to treat an "off" episode; doses should be separated by at least 2 hours
• Maximum single dose: 30 mg
• Maximum administrations per day: 5 doses per day

SUBCUTANEOUS ADMINISTRATION:
Initial dose: 2 mg (0.2 mL) subcutaneously during an "off" episode

• First dose: Obtain pulse, supine and standing blood pressure pre-dose, 20, 40, and 60 minutes post-dose; if significant hypotension is present 60 minutes post-dose, recheck after 60 minutes; if significant hypotension occurs in response to initial dose, patients should not be considered good candidates for treatment
• Titration: If initial dose is tolerated, but response is insufficient, may increase in 2 mg increments up to 6 mg (under medical supervision) or in increments of 1 mg every few days up to 3 mg (outpatient) for subsequent "off" episodes; allow at least 2 hours between doses; assess response until an effective and tolerable dose is achieved

MAINTENANCE DOSE: 2 to 6 mg subcutaneously during an "off" episode; doses should be separated by at least 2 hours; average dosing frequency in clinical trials was 3 times per day
Maximum single dose: 6 mg (0.6 mL)
Maximum dosing frequency: 5 times per day
Maximum daily dose: 20 mg (2 mL) per day

Comments:

• Antiemetic medication is recommended prior to initiating therapy because of the high incidence of nausea and vomiting; trimethobenzamide 300 mg 3 times a day starting 3 days prior to the initial dose and continued as long as necessary to control nausea and vomiting, and generally no longer than 2 months after starting apomorphine, is recommended; concomitant use of ondansetron or other 5HT3 antagonist drugs are contraindicated due to reports of profound hypotension and loss of consciousness.
• Product labeling may be consulted for more detailed initial titration steps including how to achieve an "off" state for sublingual dosing and use of test doses to arrive at an initial subcutaneous dose.
• The safety and efficacy of administering a second dose for a single OFF episode has not been systematically studied.
• This drug has been studied as an adjunct to other medications.

Use: For the acute, intermittent treatment of "OFF" episodes in patients with Parkinson's disease.

Renal Dose Adjustments

Sublingual Administration:
Mild and moderate renal impairment: No dose adjustment recommended; however, dose titration should be under medical supervision
Severe renal impairment (CrCl less than 30 mL/min): Avoid use

Subcutaneous Administration:
Mild and moderate renal impairment: Reduce test dose and initial dose to 1 mg (0.1 mL)
Severe renal impairment: Data not available

Liver Dose Adjustments

Sublingual Administration:
Mild to moderate hepatic impairment (Child-Pugh Class A and B): No adjustment recommended, however, dose titration should be under medical supervision
Severe hepatic impairment (Child-Pugh Class C): Avoid use

Subcutaneous Administration:
Mild to moderate hepatic impairment: No adjustment recommended; use with close monitoring
Severe hepatic impairment: Data not available

Dose Adjustments

Dose Interruption:

• Patients having an interruption in therapy of more than 1 week should be restarted at the 2 mg dose and gradually titrated to effect and tolerability (subcutaneous administration)

Use of Test Doses to Determine Initial Starting Dose for Subcutaneous Administration:
TEST DOSE: 2 mg (0.2 mL) subcutaneously in an OFF state

• Obtain supine and standing blood pressure and pulse pre-dose, 20, 40, and 60 minutes post-dose; if significant hypotension is present at 60 minutes post-dose, recheck after 60 minutes
• If a 2 mg test dose is tolerated, but response is inadequate, administer a 4 mg (0.4 mL) test dose subcutaneously at least 2 hours after the previous dose at the next observed OFF period
• If the 4 mg test dose is not tolerated, a 3 mg (0.3 mL) test dose may be administered during a separate OFF period at least 2 hours after the previous dose

INITIAL DOSE:

• If the 2 mg test-dose is effective and tolerated: Initial dose: 2 mg (0.2 mL) subcutaneously
• If the 3 mg test-dose is effective and tolerated: Initial dose: 2 mg (0.2 mL) subcutaneously
• If the 4 mg test-dose is effective and tolerated: Initial dose: 3 mg (0.3 mL) subcutaneously

Precautions

CONTRAINDICATIONS:

• Concomitant use of 5HT3 antagonist drugs including antiemetics (e.g. ondansetron, granisetron, dolasetron, palonosetron) and alosetron; profound hypotension and loss of consciousness has been reported when subcutaneous apomorphine was administered with a 5HT3 antagonist
• Hypersensitivity/allergic reaction to the active substance or any product excipients including a sulfite (i.e., sodium metabisulfite); angioedema or anaphylaxis may occur

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

No data available

Other Comments

Administration advice:
Sublingual Administration:

• Drink water to moisten mouth prior to dosing
• Place whole film under tongue; do not cut, chew, or swallow
• Do not swallow saliva or talk until dissolved; may take about 3 minutes to dissolve completely
• Repeat doses should be administered no sooner than 2 hours after previous dose

Subcutaneous Administration:

• For subcutaneous administration only
• Administer subcutaneously in stomach area, upper arm, or upper leg; rotate injection sites
• Initial dose and dose titrations should be performed by a healthcare provider under close medical supervision
• Patient/caregiver may self-administer once healthcare provider determines it is appropriate
• Doses should be verified in mg and mL to avoid dosing errors; the dose displayed in the dosing window is mL; doses are generally expressed in mL
• Repeat doses should be administered no sooner than 2 hours after previous dose

Preparation techniques:

• Dose is supplied via a multiple-dose pen and cartridge; pens are for single patient use only and should not be shared
• The solution is colorless; do not use if it is cloudy, green, or contains particles
• The dose is set by turning white dose knob until correct number of mL is shown in the window
• If too high a dose is showing, do not dial backwards, but continue to turn dial until it is fully turned; press the injection button fully and this will reset the dial to zero without pushing medicine out of the needle
• It is important to understand that it is possible to dial a dose even if the cartridge contains less than full dose of drug; in this case, a partial dose will be delivered, and the amount remaining to be injected will appear in the dosing window
• To avoid having insufficient drug to deliver a complete dose, patients/caregivers should be encouraged to keep records of how many doses have been delivered for each cartridge, so the cartridge can be replaced before this occurs
• Consult manufacturer product information for complete instructions with illustrations

General:

• Patients who develop clinically significant orthostatic hypotension to initial dose are generally not good candidates for therapy with this drug.
• There is no evidence to suggest that single doses greater than 6 mg (0.6 mL) provide an increased benefit and therefore are not recommended.
• This drug causes severe nausea and vomiting and therefore 98% of patients in clinical trials were premedicated with trimethobenzamide for 3 days prior to study enrollment and encouraged to continue for at least 6 weeks.
• Studies in healthy individuals have shown concomitant use of ethanol both high (0.6 g/kg) or low dose (0.3 mg/kg) causes greater decreases in blood pressure compared to ethanol alone; patients should avoid alcohol while taking this drug.

Monitoring:

• Test Dose: Measure blood pressure and pulse supine and standing before, and 20, 40, and 60 minutes post dose; if there is significant hypotension at 60 minutes, repeat after 60 minutes
• Monitor for signs and symptoms of orthostatic hypotension, especially during dose escalation
• Monitor blood pressure for orthostatic hypotension in patients taking concomitant antihypertensives or vasodilators
• Monitor for somnolence, worsening mental status or behavioral changes, impulse control, and signs and symptoms of coronary or cerebral ischemia

Patient advice:

• Patients should be instructed to read the US FDA-approved patient labeling (Patient Information and Instructions for Use).
• Patients should understand they may experience severe nausea and/or vomiting and antiemetics are generally prescribed to help with that.
• Patients should understand they may develop postural hypotension or worsening orthostatic hypotension with this drug; they should be instructed to avoid alcohol and rise slowly after sitting or lying down.
• Patients should be instructed to report hallucinations, changes in behaviors, especially if accompanied by psychosis or intense urges, palpitations, or syncope.
• Patients should be instructed to speak with their healthcare provider before discontinuing therapy.
• Male patients experiencing prolonged painful erections should seek immediate medical attention.