Important Administration Instructions

APOKYN is indicated for subcutaneous administration only [see Warnings and Precautions (5.1)] and only by a multiple-dose APOKYN Pen with supplied cartridges. The initial dose and dose titrations should be performed by a healthcare provider. Blood pressure and pulse should be measured in the supine and standing position before and after dosing.

A caregiver or patient may administer APOKYN if a healthcare provider determines that it is appropriate. Instruct patients to follow the directions provided in the Patients Instructions For Use. Because the APOKYN Pen has markings in milliliters (mL), the prescribed dose of APOKYN should be expressed in mL to avoid confusion.

Visually inspect the APOKYN drug product through the viewing window for particulate matter and discoloration prior to administration. The solution should not be used if discolored (it should be colorless), or cloudy, or if foreign particles are present. Rotate the injection site and use proper aseptic technique [see How Supplied/Storage and Handling (16) and Patient Counseling Information (17)] .

Premedication and Concomitant Medication

​Because of the incidence of nausea and vomiting with APOKYN, it is recommended that treatment with trimethobenzamide 300 mg three times a day be started 3 days prior to the initial dose of APOKYN [see Warnings and Precautions (5.2)] . Alternatively, consider starting APOKYN therapy at 0.1 mL (1 mg) and titrate based upon effectiveness and tolerance.

​If trimethobenzamide is used, it should only be continued as long as necessary to control nausea and vomiting, and generally no longer than two months after initiation of treatment with APOKYN, as trimethobenzamide increases the incidence of somnolence, dizziness, and falls in patients treated with APOKYN [see Warnings and Precautions (5.2)] .

Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron, the concomitant use of apomorphine with drugs of the 5HT 3 antagonist class including antiemetics (for example, ondansetron, granisetron, dolasetron, palonosetron) and alosetron are contraindicated [see Contraindications (4)].

Dosing Information

​The recommended starting dose of APOKYN is 0.1 mL (1 mg) to 0.2 mL (2 mg). Titrate on the basis of effectiveness and tolerance, up to a maximum recommended dose of 0.6 mL (6 mg) [see Clinical Studies (14)] .

There is no evidence from controlled trials that doses greater than 0.6 mL (6 mg) gave an increased effect Reference ID: 5002510 - 3 - and therefore, individual doses above 0.6 mL (6 mg) are not recommended. The average frequency of dosing in the development program was 3 times per day. There is limited experience with single doses greater than 0.6 mL (6 mg), dosing more than 5 times per day and with total daily doses greater than 2 mL (20 mg).

​Begin dosing when patients are in an "off" state. The initial test dose should be a 0.1 mL (1 mg) or 0.2 mL (2 mg) test dose in a setting where medical personnel can closely monitor blood pressure and pulse. Both supine and standing blood pressure and pulse should be checked pre-dose and at 20 minutes, 40 minutes, and 60 minutes post-dose (and after 60 minutes, if there is significant hypotension at 60 minutes). Patients who develop clinically significant orthostatic hypotension in response to this test dose of APOKYN should not be considered candidates for treatment with APOKYN.

​If the patient tolerates the initial test dose, and responds adequately, the starting dose should be the same as the test dose, used on an as needed basis to treat recurring "off" episodes. If needed, the dose can be increased in 0.1 mL (1 mg) increments every few days on an outpatient basis.

The general principle guiding subsequent dosing (described in detail below) is to determine that the patient needs and can tolerate a higher test dose, 0.3 mL or 0.4 mL (3 mg or 4 mg, respectively) under close medical supervision. A trial of outpatient dosing may follow (periodically assessing both efficacy and tolerability), using a dose 0.1 mL (1 mg) lower than the tolerated test dose.

​If the patient tolerates a 0.1 mL (1 mg) test dose but does not respond adequately, a test dose of 0.2 mL (2 mg) may be administered under medical supervision, at least 2 hours after the initial test dose, at the next observed "off" period. If the patient tolerates a 0.2 mL (2 mg) test dose but does not respond adequately, a test dose of 0.4 mL (4 mg) may be administered under medical supervision, at least 2 hours after the initial test dose, at the next observed "off" period. Patients who do not tolerate 0.2 mL (2 mg) may need to be titrated slowly. If the patient tolerates and responds to a test dose of 0.4 mL (4 mg), the initial maintenance dose should be 0.3 mL (3 mg) used on an as needed basis to treat recurring "off" episodes as an outpatient. If needed, the dose can be increased in 0.1 mL (1 mg) increments every few days on an outpatient basis.

If the patient does not tolerate a test dose of 0.4 mL (4 mg), a test dose of 0.3 mL (3 mg) may be administered during a separate "off" period under medical supervision, at least 2 hours after the previous dose. If the patient tolerates the 0.3 mL (3 mg) test dose, the initial maintenance dose should be 0.2 mL (2 mg) used on an as needed basis to treat existing "off" episodes. If needed, and the 0.2 mL (2 mg) dose is tolerated, the dose can be increased to 0.3 mL (3 mg) after a few days. In such a patient, the dose should ordinarily not be increased to 0.4 mL (4 mg) on an outpatient basis.

Dosing in Patients with Renal Impairment

For patients with mild and moderate renal impairment, the test dose and starting dose should be reduced to 0.1 mL (1 mg) [see Clinical Pharmacology (12.3) and Use in Specific Populations (8.6)] .

Re-treatment and Interruption in Therapy

If a single dose of APOKYN is ineffective for a particular "off" period, a second dose should not be given for that "off" episode. The efficacy of the safety of administering a second dose for a single "off" episode has not been studied systematically. Do not administer a repeat dose of APOKYN sooner than 2 hours after the last dose.

Patients who have an interruption in therapy of more than a week should be restarted on a 0.2 mL (2 mg) dose and gradually titrated to effect and tolerability.