Apomorphine Dosage

Medically reviewed by Drugs.com. Last updated on Jan 31, 2025.

Usual Adult Dose for Parkinson's Disease

APOKYN:

• Starting Dose: 1 to 2 mg (0.1 to 0.2 mL) subcutaneously during an "off" episode; titrate based on efficacy and tolerance, up to 6 mg (0.6 mL).
• As an alternative to premedication with trimethobenzamide: Consider starting at 1 mg (0.1 mL); titrate based on efficacy and tolerance.
• Maintenance Dose: 2 to 6 mg (0.2 to 0.6 mL) subcutaneously as needed to treat "off" episodes; separate doses by at least 2 hours.
• Average Dosing Frequency in Clinical Trials: 3 times a day
• Maximum Dose: 6 mg (0.6 mL)/dose

Test Doses to Determine Starting and Initial Maintenance Doses:
Initial Test Dose: 1 or 2 mg (0.1 or 0.2 mL) test dose in a setting where medical personnel can closely monitor blood pressure and pulse.

• Check supine and standing blood pressure and pulse before the dose and at 20, 40, and 60 minutes after the dose (and after 60 minutes if significant hypotension at 60 minutes).
• If clinically significant orthostatic hypotension develops in response to this test dose: Patients should not be considered candidates for treatment with this drug.

If the initial test dose is tolerated and the patient 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 1 mg (0.1 mL) increments every few days on an outpatient basis.

Subsequent Dosing: The general principle is to determine that the patient needs and can tolerate a higher test dose (3 or 4 mg [0.3 or 0.4 mL]) under close medical supervision.

• A trial of outpatient dosing may follow (periodically assessing efficacy and tolerability) using a dose 1 mg (0.1 mL) lower than the tolerated test dose.

If the patient tolerates but does not respond adequately to:

• A 1 mg (0.1 mL) test dose: A 2 mg (0.2 mL) test dose may be administered under medical supervision, at least 2 hours after the initial test dose, at the next observed "off" period.
• A 2 mg (0.2 mL) test dose: A 4 mg (0.4 mL) test dose 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 2 mg (0.2 mL) may need to be titrated slowly.

If the patient tolerates and responds to a 4 mg (0.4 mL) test dose: The initial maintenance dose should be 3 mg (0.3 mL), used on an as needed basis to treat recurring "off" episodes as an outpatient.

• If needed, increase the dose in 1 mg (0.1 mL) increments every few days on an outpatient basis.

If the patient does not tolerate a 4 mg (0.4 mL) test dose: A 3 mg (0.3 mL) test dose may be administered during a separate "off" period under medical supervision, at least 2 hours after the previous dose.

• If the patient tolerates the 3 mg (0.3 mL) test dose: The initial maintenance dose should be 2 mg (0.2 mL), used on an as needed basis to treat existing "off" episodes.
• If needed, and the 2 mg (0.2 mL) dose is tolerated: The dose can be increased to 3 mg (0.3 mL) after a few days; in such patients, the dose should generally not be increased to 4 mg (0.4 mL) on an outpatient basis.

ONAPGO:

• Daily Dosage: Determined by individualized patient titration; composed of a continuous dosage and as needed extra dose(s)
• Maximum Total Dosage (including continuous dosage and any extra dose[s]): 98 mg/day, generally administered over the waking day (e.g., 16 hours)

Continuous Dosage:

• Initial continuous dosage (continuous infusion): 1 mg/hour subcutaneously
• Titration of continuous dosage: Titrate as needed in 0.5 to 1 mg/hour increments.
• Dose adjustments may be made daily (or at longer intervals) through the titration process.
• Mean dosage in clinical trials: 4 mg/hour subcutaneously
• Maximum continuous dosage: 6 mg/hour administered over the waking day (e.g., 16 hours)

Extra Dose:

• Titrate to clinical response and tolerability.
• Adjustments: In 0.5 or 1 mg increments
• Subsequent extra doses: Between 0.5 and 2 mg
• No more than 3 extra doses per day over 16 hours with at least 3 hours between each dose

Comments:

• Premedication: Due to the incidence of nausea and vomiting, start trimethobenzamide (300 mg orally 3 times a day) 3 days before the initial dose of this drug.
• As an alternative to premedication (i.e., without antiemetics): Consider starting APOKYN at 1 mg (0.1 mL) OR consider starting ONAPGO at 1 mg/hour and titrate based on efficacy and tolerance.
• If used, trimethobenzamide should be continued only as long as necessary to control nausea and vomiting, and generally no longer than 2 months after starting apomorphine; trimethobenzamide increases the incidence of somnolence, dizziness, and falls in patients treated with apomorphine.
• APOKYN: Because the pen has markings in "mL", the prescribed dose of this drug should be expressed in "mL" to avoid confusion.
• ONAPGO:
• The prescribed dose should be expressed in "mg/hr" for the continuous dosage and "mg" for an extra dose.
• After starting this drug, adjustment of concomitant anti-Parkinson's disease medications may be needed.
• Extra doses may be used upon starting in the morning, when restarting the continuous dosage after a 1-hour or longer break in use (i.e., as a loading dose), or as a supplement to the continuous dosage to manage acute uncontrolled "off" symptoms.
• If 3 extra doses are routinely required during daily infusion, further adjustment of the continuous dosage should be considered.
• This drug is not substitutable for apomorphine products intended for intermittent use.
• Insufficient information is available regarding concomitant use of other apomorphine-containing products with this drug.

Uses:

• APOKYN: 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
• ONAPGO: For the treatment of motor fluctuations in patients with advanced Parkinson's disease

Renal Dose Adjustments

APOKYN:

• Mild or moderate renal dysfunction: Reduce the test dose and starting dose to 1 mg (0.1 mL).
• Severe renal dysfunction: Data not available

ONAPGO:

• Mild or moderate renal dysfunction:
• Initial extra dose: 0.5 to 1 mg (should not exceed 1 mg)
• Continuous dose, maximum daily dose, or subsequent extra doses (after initial extra dose): No adjustment recommended
• Severe renal dysfunction: Data not available

Comments:

• AUC and Cmax were increased in patients with mild or moderate renal dysfunction.
• Patients with severe renal dysfunction have not been studied.

Liver Dose Adjustments

Mild and moderate liver dysfunction: Caution recommended.
Severe liver dysfunction: Data not available

Comments:

• Patients with mild and moderate liver dysfunction should be monitored closely; AUC and Cmax were increased in these patients.
• Patients with severe liver dysfunction have not been studied.

Dose Adjustments

APOKYN:
Retreatment and Interruption in Therapy:

• If a single dose is ineffective for a particular "off" period: Do not administer a second dose for that "off" episode.
• The safety and efficacy of using a second dose for a single "off" episode has not been systematically studied.
• Do not administer a repeat dose of this drug sooner than 2 hours after the last dose.
• If therapy is interrupted for more than a week: Restart at 2 mg (0.2 mL) and gradually titrate to effect and tolerability.

Precautions

CONTRAINDICATIONS:

• Concomitant use of the 5-HT3 antagonist class including antiemetics (e.g., ondansetron, granisetron, dolasetron, palonosetron) and alosetron
• Hypersensitivity/allergic reaction to the active component or any of the ingredients, including a sulfite (i.e., sodium metabisulfite)

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

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:
APOKYN:

• For subcutaneous administration only
• A health care provider should perform the initial dose and dose titrations.
• Measure blood pressure and pulse in the supine and standing positions before and after dosing.
• A caregiver or patient may administer this drug if a health care provider determines it is appropriate.
• Instruct patients to follow the directions provided in the Instructions for Use.
• Administer subcutaneously in the stomach area (at least 2 inches from the navel), upper arm, or upper thigh; rotate the injection site with each injection.

ONAPGO:

• For subcutaneous use by infusion only; administer with the ONAPGO pump.
• Initiation and dose titrations should be done under medical supervision.
• Patients selected for treatment with this drug should be capable of understanding and trained on using the delivery system, either themselves or with the assistance of a caregiver.
• Before first use, educate and train patients and caregivers on the proper use of this drug and the device delivery system.
• Administer subcutaneously in 1 of the following areas: abdomen (at least 2 inches from the navel), top of thigh, lower back, or upper back (only when infusion site is prepared by a caregiver or health care provider).
• Change the infusion site every day; do not select an infusion site that is bruised, has bumps/nodules, or is irritated.
• Use a new single-dose cartridge and cartridge holder each day; discard unused portion.
• If possible, taper before discontinuing; sudden discontinuation or rapid dose reduction could cause increased severity of Parkinson's disease motor symptoms.

Storage requirements:

• Store at 20C to 25C (68F to 77F); excursions permitted to 15C to 30C (59F to 86F).

Reconstitution/preparation techniques:

• The manufacturer product information should be consulted.

General:

• Profound hypotension and loss of consciousness have been reported when this drug was administered with ondansetron; coadministration with 5-HT3 antagonists is contraindicated.
• This drug contains sodium metabisulfite, which may cause allergic-type reactions (including anaphylactic symptoms and life-threatening or less severe asthmatic episodes) in certain susceptible patients.
• APOKYN:
• This drug has been studied as an adjunct to other medications.
• There is no evidence that doses greater than 6 mg (0.6 mL) increase effect; therefore, such doses are not recommended.
• There is limited experience with single doses greater than 6 mg (0.6 mL), dosing more than 5 times per day, and with total daily doses greater than 20 mg (2 mL).

Monitoring:

• Cardiovascular: For signs/symptoms of orthostatic hypotension in patients taking dopaminergic agonists (during therapy, especially dose escalation)

Patient advice:

• Read the US FDA-approved patient labeling (Patient Information and Instructions for Use).
• This drug is intended for subcutaneous injection only; do not administer IV (risk of serious complications [e.g., thrombus formation/pulmonary embolism due to crystallization]).
• If you have a sulfite sensitivity, various allergic-type reactions (including anaphylactic symptoms and life-threatening asthmatic attacks) may occur; if you have any hypersensitivity/allergic reaction (characterized by urticaria, rash, pruritus, and/or various manifestations of angioedema) to this drug, do not take it again.
• Taking this drug with trimethobenzamide may increase the risks for somnolence, dizziness, and falls; consult your health care provider before stopping trimethobenzamide.
• Sedating effects (including somnolence and falling asleep while engaged in activities of daily living) have been reported; do not drive a car or engage in other potentially dangerous activities until you have had enough experience to determine whether or not it adversely affects your mental and/or motor performance.
• If increased somnolence or episodes of falling asleep during activities of daily living (e.g., watching television, passenger in a car) occur, do not drive or participate in potentially dangerous activities until you have contacted your physician.
• Due to possible additive effects of alcohol use, limit your alcohol intake.
• Hypotension and/or orthostatic symptoms (e.g., dizziness, nausea, syncope, sometimes sweating) may occur, more often during initial therapy or with an increase in dose at any time; rise slowly after sitting or lying down after taking this drug.
• Because alcohol and nitroglycerin (and possibly other vasodilators and antihypertensive medications) may worsen the hypotensive effect of this drug, it is preferable to lie down before taking sublingual nitroglycerin and to remain supine and avoid standing for at least 45 minutes after nitroglycerin; avoid alcohol while using this drug.
• If you have a major psychotic disorder, normally you should not use this drug due to the risk of exacerbating the psychosis; many treatments for psychosis may decrease the efficacy of this drug.
• Contact your health care provider if any signs/symptoms of hemolytic anemia develop.
• Seek medical attention immediately if a prolonged painful erection occurs.
• If taking APOKYN, contact your health care provider if you wish to discontinue or decrease the dose of this drug.

Further information

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