Apokyn

Anti-Parkinson Agents, Dopamine Agonists

Hazardous Drugs Classification
NIOSH 2016 List: Group 2
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
INJECTABLE: Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
ORAL: Use gloves to handle. Manipulating film will increase exposure and require additional protective equipment.

Oral Administration Other Oral Formulations

Sublingual Administration (e.g., Kynmobi sublingual film)
For sublingual administration only.
Dose initiation should be supervised by a health care provider in a setting where blood pressure and pulse can be monitored. If dose titration is required, administer under the supervision of a health care provider until an effective and tolerable dose is achieved.
Keep the sublingual film in the foil pouch until ready to use.
Must administer whole. Do not cut, chew, or swallow the film.
After placement under the tongue, the film will disintegrate in about 3 minutes.
Doses should be separated by at least 2 hours.
Due to a high incidence of nausea and vomiting from apomorphine, treatment with the antiemetic trimethobenzamide may be administered as needed, prior to, or during treatment with apomorphine. If premedicating for nausea or vomiting is needed, trimethobenzamide may be started 3 days prior to the first dose of apomorphine. Continue trimethobenzamide as long as needed to control nausea and vomiting, and generally no longer than 2 months because trimethobenzamide increases the incidence of somnolence, dizziness, and falls when administered with apomorphine.
Contact the health care provider if the patient's symptoms do not respond to the first dose for a particular 'off' episode. Do not use a second dose for that episode.

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Do not use injections which are unusually viscous, cloudy, or discolored. Always inspect the vial or pre-filled cartridge to be sure the liquid is clear and does not contain particles.

Subcutaneous Administration

For subcutaneous administration only. Do not inject intramuscularly or intravenously.
Initiation of apomorphine treatment requires a test dose procedure to determine dosage titration.
Because of the high incidence of nausea/vomiting from apomorphine, the manufacturer recommends trimethobenzamide 300 mg PO 3 times per day be administered for 3 days prior to the first apomorphine injection. Treatment with trimethobenzamide should be continued as long as necessary to control nausea and vomiting, but generally no longer than 2 months duration after treatment initiation with apomorphine because trimethobenzamide increases the incidence of somnolence, dizziness, and falls in patients treated with apomorphine.
Because the apomorphine Pen is marked in milliliters (mL), the prescribed dose should be expressed in mL to avoid prescription errors.
Skin contact with apomorphine injection may cause an allergic skin reaction in some people. Wash hands thoroughly before and after handling this medication.
Patients and/or caregivers who are advised to administer apomorphine in medically unsupervised situations should receive instruction on the proper use of the product from the physician or other suitably qualified health care professional. The patient should be observed during the initial dosing (see Patient Monitoring, below).
Interruption of treatment: If the patient has not received an apomorphine injection in more than 1 week, re-institute by implementing the initial test dosage and titration instructions recommended by the manufacturer.
 
Preparation of dosage:
Ampules: Syringes may be filled from the ampules the night before use and stored in the refrigerator until the next day.
Apomorphine dosing pen (Apokyn Pen): The pen is dosed in milliliters (mL), not milligrams (mg). For example, a 1 mg dose is equal to a volume of 0.1 mL on the dosing pen. The pen allows for dialing in of the patient's usual dose, even if there is not enough medicine in the pen to do so. If there is not enough medicine for the usual dose, the device must be 're-armed' and the remaining amount needed should be dialed in. This process should be avoided if possible in order to avoid dosage errors. Consider keeping a record of doses used, so the cartridges can be replaced appropriately.
 
Subcutaneous (SC) Injection of dosage:
Do not inject apomorphine into infected, erythematous, or irritated areas of the skin.
Double-check dosage in syringe prior to administration.
Aspirate prior to injection to avoid injection into a blood vessel; inject subcutaneously taking care not to inject intradermally.
Rotate administration sites with each injection (e.g., abdomen, upper arm, thigh) to reduce the incidence of a skin reaction.
 
Patient monitoring during and after the injection:
During the test dosing to determine dose titration, the blood pressure should be closely monitored (pre-dose, and 20, 40, and 60 minutes after the injection).
Monitor for patient response to the injection (i.e., reduction in 'off' episode symptoms).
Contact the health care provider if the patient's symptoms do not respond to the first dose for a particular 'off' episode. Do not use a second dose for that episode.
If the patient has not received an apomorphine injection in more than 1 week, must re-institute following the initial test dosage and titration instructions recommended by the manufacturer.

Severe

cardiac arrest / Early / 4.0-4.0
myocardial infarction / Delayed / 4.0-4.0
heart failure / Delayed / 5.0
torsade de pointes / Rapid / Incidence not known
macular degeneration / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
hemolytic anemia / Delayed / Incidence not known

Moderate

dyskinesia / Delayed / 24.0-35.0
orthostatic hypotension / Delayed / 0-20.0
angina / Early / 15.0-15.0
chest pain (unspecified) / Early / 15.0-15.0
hallucinations / Early / 6.0-14.0
hypotension / Rapid / 0-10.0
confusion / Early / 0-10.0
edema / Delayed / 10.0-10.0
peripheral edema / Delayed / 10.0-10.0
stomatitis / Delayed / 2.0-7.0
erythema / Early / 7.0-7.0
oral ulceration / Delayed / 2.0-7.0
priapism / Early / 0-1.0
dyspnea / Early / 5.0
depression / Delayed / 5.0
constipation / Delayed / 5.0
dehydration / Delayed / 5.0
sudden sleep onset / Delayed / Incidence not known
palpitations / Early / Incidence not known
QT prolongation / Rapid / Incidence not known
contact dermatitis / Delayed / Incidence not known
delirium / Early / Incidence not known
impulse control symptoms / Delayed / Incidence not known

Mild

yawning / Early / 40.0-40.0
drowsiness / Early / 13.0-35.0
nausea / Early / 13.0-31.0
injection site reaction / Rapid / 26.0-26.0
rhinorrhea / Early / 7.0-20.0
dizziness / Early / 9.0-20.0
ecchymosis / Delayed / 5.0-16.0
paresthesias / Delayed / 0-13.0
vomiting / Early / 1.0-11.0
fatigue / Early / 5.0-7.0
headache / Early / 5.0-6.0
xerostomia / Early / 6.0-6.0
hyperhidrosis / Delayed / 5.0-6.0
syncope / Early / 2.0-2.0
pruritus / Rapid / 2.0-2.0
insomnia / Early / 5.0
infection / Delayed / 5.0
anxiety / Delayed / 5.0
diarrhea / Early / 5.0
weakness / Early / 5.0
musculoskeletal pain / Early / 5.0
arthralgia / Delayed / 5.0
back pain / Delayed / 5.0
flushing / Rapid / Incidence not known
pallor / Early / Incidence not known
paranoia / Early / Incidence not known
agitation / Early / Incidence not known
libido increase / Delayed / Incidence not known
rash / Early / Incidence not known
urticaria / Rapid / Incidence not known

Apokyn, KYNMOBI

Rx

Non-narcotic morphine derivative; dopamine agonist with potent emetic properties
Approved as a sublingual film for acute, intermittent 'off' episodes associated with Parkinson's disease; subcutaneous injection approved in advanced Parkinson's disease
Monitor for hypotension, orthostasis, new or worsening impulse control symptoms, and patient reports of sudden sleep onset
Concurrent treatment with an antiemetic (e.g., trimethobenzamide) is recommended; use with 5-HT3 antagonists is contraindicated

For the treatment of acute, intermittent 'off' episodes associated with Parkinson's disease. For the treatment of acute, intermittent treatment of 'off' episodes in patients with advanced Parkinson's disease. Subcutaneous dosage (e.g., Apokyn injection) Adults

Because the apomorphine pen is marked in milliliters (mL), the prescribed dose should be expressed in mL to avoid prescription errors. Initially, administer 0.1 mL (1 mg) to 0.2 mL (2 mg) subcutaneously as a test dose in a setting where blood pressure (BP) can be closely monitored by medical staff (check BP pre-dose and 20, 40, and 60 minutes after the dose). If tolerated and the patient responds, use the same starting dose that was given as a test dose on an as needed basis. Dosage may be increased by 1 mg every few days, not to exceed 0.6 mL (6 mg). If the test dose of 0.1 mL (1 mg) is tolerated but the patient does not respond, administer a test dose of 0.2 mL (2 mg) no sooner than 2 hours after the 0.1 mL (1 mg) test dose, where BP can be closely monitored by medical staff (pre-dose and 20, 40, and 60 minutes after the dose). Patients who do not tolerate the 0.2 mL (2 mg) dose may require a slower titration. If the patient tolerates the 0.2 mL (2 mg) test dose but does not respond, administer a test dose of 0.4 mL (4 mg) under close monitoring by medical staff. Give no sooner than 2 hours after the initial test dose, at the next observed "off" period. If the 0.4 mL (4 mg) test dose is tolerated, the starting dose should be 0.3 mL (3 mg) subcutaneously; dosage may be increased by 1 mg every few days as required, not to exceed 0.6 mL (6 mg). If the 0.4 mL (4 mg) test dose is not tolerated, administer a test dose of 0.3 mL (3 mg) during a separate "off" period no sooner than 2 hours after the 0.4 mL (4 mg) test dose where BP can be closely monitored by medical staff (pre-dose and 20, 40, and 60 minutes after the dose). If the 0.3 mL (3 mg) test dose is tolerated, begin with 0.2 mL (2 mg) subcutaneously; dosage may be increased by 0.1 mL (1 mg) every few days as required but generally should not exceed 0.4 mL (4 mg) as an outpatient. Most patients studied in the apomorphine development program responded to 0.3 mL to 0.6 mL (3 mg to 6 mg per dose). There is no evidence from controlled trials that single doses higher than 0.6 mL (6 mg) give an increased effect, and thus higher doses are not recommended. The average frequency of dosing was 3 times per day in the development program. Max Single Dose: 0.6 mL (6 mg), Max Dosing Frequency: 5 times per day. Usual Max Daily Dose: 2 mL/day (20 mg/day). Because of the high incidence of nausea/vomiting from apomorphine, the manufacturer recommends initiating trimethobenzamide 300 mg PO 3 times per day, starting 3 days prior to the first apomorphine injection; continue trimethobenzamide as long as necessary to control nausea and vomiting, but generally no longer than 2 months duration since trimethobenzamide increases the incidence of somnolence, dizziness, and falls in patients treated with apomorphine.

Sublingual dosage (e.g., Kynmobi film) Adults

Initially, 10 mg SL when the patient is in an 'off' state and in a setting where a health care provider can monitor blood pressure and pulse. If the 10 mg dose is tolerated and the response is adequate, the 10 mg dose is used on an as-needed basis, up to 5 times per day. If the dose is tolerated, but the response is insufficient, the patient's usual Parkinson's medications should be resumed and upward titration with apomorphine continued generally within 3 days. Increases should occur in 5 mg increments along with an assessment of response. Continue to titrate in a similar manner, under the supervision of a health care provider, until an effective and tolerated dose is achieved. Dose Range: 10 to 30 mg SL per dose. Max Single Dose: 30 mg SL. Max Daily Frequency: 5 doses per day. Separate doses by at least 2 hours. If a single dose is ineffective for a particular 'off' episode, a second dose should not be given for that particular 'off' episode because the safety and efficacy of this dosing strategy have not been studied. Because of the high incidence of nausea/vomiting from apomorphine, the antiemetic trimethobenzamide 300 mg PO 3 times daily may be given as needed, prior to, or during treatment. If pretreatment is needed, trimethobenzamide may be started 3 days prior to the first apomorphine dose and continued as long as necessary. In general, trimethobenzamide treatment should be no longer than 2 months due to the increased incidence of somnolence, dizziness, and falls in patients treated with apomorphine.

For use in the differential diagnosis of idiopathic parkinsonism† and as a diagnostic test for dopaminergic responsiveness in parkinsonian syndromes† to determine whether a patient will respond or is still responsive to levodopa therapy.
NOTE: To reduce the incidence of adverse effects (emesis) from apomorphine injection, one study suggests the following: domperidone 20 mg PO three times per day for 2—3 days prior to the administration of apomorphine and domperidone 20 mg PO three times per day during the day of apomorphine administration beginning 30—60 minutes prior to the apomorphine dose. Domperidone is not available in the United States; data are not available on the use of trimethobenzamide for this indication.

NOTE: The dose of SC apomorphine should be expressed in ml to avoid prescription dosing errors. Subcutaneous dosage Adults

The initial dose is 0.1 mL (1 mg) subcutaneously. If a positive response is not obtained, give a 0.2 mL (2 mg) subcutaneous dose at least 30 minutes after the initial dose. Then, if no response, give 0.4 mL (4 mg) subcutaneously at least 30 minutes after the second dose. Still, if no response, give 0.5 mL (5 mg) subcutaneously at least 30 minutes after the third dose. Increase dose until a positive response is recorded (up to 1 mL or 10 mg) with at least 30 minutes between each increase in dose. NOTE: Doses > 0.6 mL (6 mg) subcutaneously may pose a greater risk of QTc interval prolongation.

†Indicates off-label use

Hepatic Impairment

Sublingual Film
Mild or moderate hepatic impairment (Child-Pugh Classes A and B): No dosage adjustment is needed; however, because of the potential for increased exposure, titrate under medical supervision.
Severe hepatic impairment (Child-Pugh Class C): Avoid use.
 
Subcutaneous Injection
Use with caution in hepatic impairment. A dose reduction may be warranted; however, specific guidelines are not available. Patients with severe hepatic impairment have not been evaluated.

Renal Impairment

Sublingual Film
Mild or moderate renal impairment (CrCl 30 to 80 mL/minute): No dosage adjustment is needed; however, because of the potential for increased exposure, titrate under medical supervision.
Severe renal impairment (CrCl less than 30 mL/minute): Avoid use.
 
Subcutaneous Injection
Mild to moderate renal impairment: The test dose and starting dose is 1 mg (0.1 mL).
Severe renal impairment: Apomorphine has not been evaluated.

Abarelix: (Major) Use apomorphine and abarelix together with caution due to the risk of additive QT prolongation. Abarelix has a risk of QT prolongation and dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and diphenhydramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking apomorphine. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Acetaminophen; Chlorpheniramine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and chlorpheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and chlorpheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and chlorpheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and chlorpheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and chlorpheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Acetaminophen; Codeine: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking apomorphine. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and doxylamine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Acetaminophen; Diphenhydramine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and diphenhydramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Acetaminophen; Hydrocodone: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking apomorphine. Limit the use of opioid pain medications with entacapone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Acetaminophen; Oxycodone: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Adagrasib: (Major) Concomitant use of adagrasib and apomorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Alfentanil: (Major) Apomorphine may cause additive sedation or hypotension with alfentanil. Monitor patients receiving alfentanil with other CNS depressants for hypotension and prolonged respiratory depression and sedation. In such cases of combined treatment, a dose reduction of one or both agents may be necessary.
Alfuzosin: (Moderate) Use apomorphine and alfuzosin together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Alfuzosin may prolong the QT interval in a dose-dependent manner.
Aliskiren: (Moderate) Use of aliskiren and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Use of aliskiren and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Alprazolam: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and benzodiazepines could result in additive depressant effects.
Amiodarone: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval, including apomorphine, should only be done after careful assessment of risks versus benefits. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Amisulpride: (Major) Use apomorphine and amisulpride together with caution due to the risk of additive QT prolongation. Monitor ECGs for QT prolongation when amisulpride is administered with apomorphine. Amisulpride causes dose- and concentration- dependent QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Amitriptyline: (Moderate) Use apomorphine and tricyclic antidepressants together with caution due to the risk of additive QT prolongation. Tricyclic antidepressants have been associated with QT prolongation, primarily in overdosage or when excessive plasma concentrations are encountered. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Additive sedation is also possible during combined use of these agents.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of clarithromycin with apomorphine when possible. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Anagrelide: (Major) Use apomorphine and anagrelide together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Torsades de pointes (TdP) and ventricular tachycardia have been reported during postmarketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary.
Angiotensin II receptor antagonists: (Moderate) Use of angiotensin II receptor antagonists and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Angiotensin-converting enzyme inhibitors: (Moderate) Use of angiotensin-converting enzyme inhibitors (ACE inhibitors) and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects. A reduction in the dose of one or both drugs should be considered to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Aripiprazole: (Moderate) Use apomorphine and aripiprazole with caution due to a risk for QT prolongation and sedation. Apomorphine and aripiprazole may decrease the effectiveness of each other due to opposing effects on dopamine. Additive CNS effects are also possible. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. In general, atypical antipsychotics are less likely to interfere with Parkinson's disease treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, sedation, fast, irregular heartbeat, and diminished effectiveness of either agent during coadministration.
Arsenic Trioxide: (Major) Concurrent use of arsenic trioxide and apomorphine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If possible, apomorphine should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Artemether; Lumefantrine: (Major) Concurrent use of apomorphine and artemether; lumefantrine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Consider ECG monitoring if apomorphine must be used with or after artemether; lumefantrine treatment. Administration of artemether; lumefantrine is associated with prolongation of the QT interval. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Asenapine: (Major) Avoid use of apomorphine and asenapine together if possible due to a risk for additive QT prolongation and sedation. Also, apomorphine and asenapine can reduce the effectiveness of each other through opposing effects on dopamine. Addtive CNS effects are also possible. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Asenapine has been associated with QT prolongation. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents also known to cause QT prolongation, such as apomorphine. In general, atypical antipsychotics are less likely to interfere with Parkinson's disease treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, sedation, fast, irregular heartbeat, and diminished effectiveness of either agent if coadministration cannot be avoided.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
Aspirin, ASA; Carisoprodol: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking apomorphine. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Atomoxetine: (Moderate) Concomitant use of atomoxetine and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Azithromycin: (Major) Avoid coadministration of azithromycin with apomorphine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Baclofen: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
Barbiturates: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
Bedaquiline: (Major) Use apomorphine and bedaquiline together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Bedaquiline has been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
Belladonna; Opium: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Benzodiazepines: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and benzodiazepines could result in additive depressant effects.
Beta-adrenergic blockers: (Moderate) Use of beta blockers and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Brexpiprazole: (Moderate) Due to mutually opposing effects on dopamine, brexpiprazole and apomorphine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with Parkinson's disease treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, sedation, and diminished effectiveness of either agent during coadministration.
Brompheniramine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and brompheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and brompheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Brompheniramine; Phenylephrine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and brompheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Brompheniramine; Pseudoephedrine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and brompheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and brompheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Buprenorphine: (Major) Use apomorphine and buprenorphine together with caution due to the risk of additive QT prolongation and CNS depression. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). The FDA-approved labeling for some buprenorphine products recommend avoiding use with any drug that has the potential to prolong the QT interval, such as apomorphine. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Buprenorphine; Naloxone: (Major) Use apomorphine and buprenorphine together with caution due to the risk of additive QT prolongation and CNS depression. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). The FDA-approved labeling for some buprenorphine products recommend avoiding use with any drug that has the potential to prolong the QT interval, such as apomorphine. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking apomorphine. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking apomorphine. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Cabotegravir; Rilpivirine: (Moderate) Exercise caution when administering apomorphine concomitantly with rilpivirine since concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Calcium-channel blockers: (Moderate) Use of calcium-channel blockers and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and apomorphine. CNS depressants can potentiate the effects of cannabidiol.
Capsaicin; Metaxalone: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
Carbinoxamine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and carbinoxamine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Cariprazine: (Moderate) Due to mutually opposing effects on dopamine, cariprazine and apomorphine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with Parkinson's disease treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, sedation, and diminished effectiveness of either agent during coadministration.
Carisoprodol: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
Celecoxib; Tramadol: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and apomorphine. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as apomorphine, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Central-acting adrenergic agents: (Moderate) Use of central-acting adrenergic agents and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Ceritinib: (Major) Avoid coadministration of ceritinib with apomorphine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with apomorphine should generally be avoided because of the possibility of additive sedative effects. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with apomorphine should generally be avoided because of the possibility of additive sedative effects. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and dexchlorpheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Chlorcyclizine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and chlorcyclizine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Chlordiazepoxide: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and benzodiazepines could result in additive depressant effects.
Chlordiazepoxide; Amitriptyline: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and benzodiazepines could result in additive depressant effects. (Moderate) Use apomorphine and tricyclic antidepressants together with caution due to the risk of additive QT prolongation. Tricyclic antidepressants have been associated with QT prolongation, primarily in overdosage or when excessive plasma concentrations are encountered. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Additive sedation is also possible during combined use of these agents.
Chlordiazepoxide; Clidinium: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and benzodiazepines could result in additive depressant effects.
Chloroquine: (Major) Avoid coadministration of chloroquine with apomorphine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes; the risk of QT prolongation is increased with higher chloroquine doses. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Chlorpheniramine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and chlorpheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Chlorpheniramine; Codeine: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking apomorphine. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and chlorpheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Chlorpheniramine; Dextromethorphan: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and chlorpheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and chlorpheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and chlorpheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking apomorphine. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and chlorpheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking apomorphine. Limit the use of opioid pain medications with entacapone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and chlorpheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and chlorpheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Chlorpheniramine; Phenylephrine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and chlorpheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Chlorpheniramine; Pseudoephedrine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and chlorpheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Chlorpromazine: (Major) Avoid use of apomorphine with chlorpromazine due to an increased risk for QT prolongation and torsade de pointes (TdP). Also, the effectiveness of either agent may be decreased due to opposing effects on dopamine; consider if an atypical antipsychotic would be a suitable alternative to chlorpromazine. Additive CNS depression is also possible. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP at therapeutic doses. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Chlorzoxazone: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
Ciprofloxacin: (Moderate) Concomitant use of ciprofloxacin and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Cisapride: (Contraindicated) Because of the potential for torsade de pointes (TdP), apomorphine use is contraindicated with cisapride. Cisapride has a known risk for QT prolongation and is contraindicated for use with other drugs that may cause QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Citalopram: (Major) Concomitant use of apomorphine and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clarithromycin: (Major) Avoid coadministration of clarithromycin with apomorphine when possible. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Clemastine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and clemastine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Clofazimine: (Moderate) Concomitant use of clofazimine and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Clomipramine: (Moderate) Use apomorphine and tricyclic antidepressants together with caution due to the risk of additive QT prolongation. Tricyclic antidepressants have been associated with QT prolongation, primarily in overdosage or when excessive plasma concentrations are encountered. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Additive sedation is also possible during combined use of these agents.
Clonazepam: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and benzodiazepines could result in additive depressant effects.
Clorazepate: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and benzodiazepines could result in additive depressant effects.
Clozapine: (Moderate) Coadministration of apomorphine and clozapine may increase the risk for QT prolongation or sedation. Apomorphine and clozapine may decrease the effectiveness of each other due to opposing effects on dopamine. Additive CNS effects are also possible. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. In general, atypical antipsychotics are less likely to interfere with Parkinson's disease treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, sedation, fast, irregular heartbeat, and diminished effectiveness of either agent if coadministration cannot be avoided.
Codeine: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking apomorphine. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Codeine; Guaifenesin: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking apomorphine. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking apomorphine. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking apomorphine. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Moderate) Use promethazine with apomorphine with caution; avoid use if possible due to an increased risk for QT prolongation and sedation. Promethazine and apomorphine may reduce the effectiveness of each other through opposing effects on dopamine. Apomorphine causes considerable somnolence, and concomitant administration of apomorphine and CNS depressants like promethazine could result in additive CNS effects. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Promethazine is associated with a possible risk for QT prolongation.
Codeine; Promethazine: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking apomorphine. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Moderate) Use promethazine with apomorphine with caution; avoid use if possible due to an increased risk for QT prolongation and sedation. Promethazine and apomorphine may reduce the effectiveness of each other through opposing effects on dopamine. Apomorphine causes considerable somnolence, and concomitant administration of apomorphine and CNS depressants like promethazine could result in additive CNS effects. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Promethazine is associated with a possible risk for QT prolongation.
Crizotinib: (Major) Avoid coadministration of crizotinib with apomorphine due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Cyclobenzaprine: (Moderate) Monitor for additive CNS effects if apomorphine is used concurrently with tricyclic antidepressants. Apomorphine causes considerable somnolence, and concomitant administration of apomorphine and CNS agents like cyclobenzaprine could result in additive CNS effects.
Cyproheptadine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and cyproheptadine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Dantrolene: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
Dasatinib: (Moderate) Use apomorphine and dasatinib together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
Degarelix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving apomorphine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Desflurane: (Major) Use apomorphine and halogenated anesthetics together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Halogenated anesthetics can prolong the QT interval. In addition, concomitant administration of apomorphine and halogenated anesthetics could also result in additive depressant effects.
Desipramine: (Moderate) Use apomorphine and tricyclic antidepressants together with caution due to the risk of additive QT prolongation. Tricyclic antidepressants have been associated with QT prolongation, primarily in overdosage or when excessive plasma concentrations are encountered. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Additive sedation is also possible during combined use of these agents.
Deutetrabenazine: (Moderate) Use apomorphine and deutetrabenazine together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Also, monitor for excessive sedation and somnolence during coadministration of apomorphine and deutetrabenazine. Concurrent use may result in additive CNS depression.
Dexchlorpheniramine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and dexchlorpheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and dexchlorpheniramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Dexmedetomidine: (Moderate) Concomitant use of dexmedetomidine and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and diphenhydramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Dextromethorphan; Quinidine: (Major) Use apomorphine and quinidine together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Quinidine administration is associated with QT prolongation and torsades de pointes.
Diazepam: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and benzodiazepines could result in additive depressant effects.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Dimenhydrinate: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and dimenhydrinate could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Diphenhydramine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and diphenhydramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Diphenhydramine; Ibuprofen: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and diphenhydramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Diphenhydramine; Naproxen: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and diphenhydramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Diphenhydramine; Phenylephrine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and diphenhydramine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Disopyramide: (Major) Use apomorphine and disopyramide together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP).
Dofetilide: (Major) Coadministration of dofetilide and apomorphine is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Dolasetron: (Contraindicated) The concurrent use of apomorphine and serotonin-receptor antagonists is contraindicated due to the possibility of an excessive lowering of blood pressure and unconsciousness. Additionally, additive QT prolongation is possible during coadministration of apomorphine with dolasetron, granisetron, and ondansetron.
Dolutegravir; Rilpivirine: (Moderate) Exercise caution when administering apomorphine concomitantly with rilpivirine since concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Donepezil: (Moderate) Use apomorphine and donepezil together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy.
Donepezil; Memantine: (Moderate) Use apomorphine and donepezil together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy.
Doxazosin: (Moderate) Use of doxazosin and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Doxepin: (Moderate) Use apomorphine and tricyclic antidepressants together with caution due to the risk of additive QT prolongation. Tricyclic antidepressants have been associated with QT prolongation, primarily in overdosage or when excessive plasma concentrations are encountered. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Additive sedation is also possible during combined use of these agents.
Doxylamine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and doxylamine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Doxylamine; Pyridoxine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and doxylamine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Dronabinol: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants, such as dronabinol, could result in additive depressant effects. Careful monitoring is recommended during combined use of a CNS depressant and apomorphine. A dose reduction of one or both drugs may be warranted.
Dronedarone: (Contraindicated) The concomitant use of dronedarone with other drugs that prolong the QTc may induce torsade de pointes (TdP) and is contraindicated. Dronedarone is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Droperidol: (Major) Any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with apomorphine since concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with apomorphine since concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with apomorphine since concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Dose-related QTc prol

ongation is associated with therapeutic apomorphine exposure.
Eliglustat: (Moderate) Exercise caution when administering apomorphine concomitantly with eliglustat since concurrent use may increase the risk of QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Exercise caution when administering apomorphine concomitantly with rilpivirine since concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Exercise caution when administering apomorphine concomitantly with rilpivirine since concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Encorafenib: (Major) Avoid coadministration of encorafenib and apomorphine due to a possible increased risk of QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Entrectinib: (Major) Avoid coadministration of entrectinib with apomorphine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Eplerenone: (Moderate) Use of eplerenone and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Eribulin: (Major) Use apomorphine and eribulin together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Eribulin has been associated with QT prolongation. ECG monitoring is recommended if eribulin is administered with apomorphine.
Erythromycin: (Major) Concomitant use of apomorphine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Escitalopram: (Moderate) Concomitant use of escitalopram and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Esketamine: (Major) Because of the possibility of additive sedative effects, caution is advisable during concurrent use of dopaminergic agents, such as apomorphine, and CNS depressants, such as esketamine. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients who have received a dose of esketamine should be instructed not to drive or engage in other activities requiring complete mental alertness until the next day after a restful sleep.
Estazolam: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and benzodiazepines could result in additive depressant effects.
Ethanol: (Major) Advise patients to avoid alcohol-containing beverages during apomorphine therapy. Concurrent use of alcohol and apomorphine has resulted in significantly worse orthostatic hypotension compared to apomorphine alone. Coadministration of low dose ethanol (0.3 grams/kg) with subcutaneous apomorphine in healthy subjects did not have a significant effect on the pharmacokinetics of apomorphine; however, high dose alcohol (0.6 grams/kg), equivalent to about 3 standardized alcohol-containing beverages, increased the maximum concentration of apomorphine by about 63%. A similar study with sublingual apomorphine has not been conducted.
Etomidate: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and apomorphine. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as apomorphine, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Fentanyl: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Fingolimod: (Moderate) Exercise caution when administering apomorphine concomitantly with fingolimod since concurrent use may increase the risk of QT prolongation. Fingolimod may cause a decreased heart rate and prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Flecainide: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering flecainide with apomorphine. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Fluconazole: (Moderate) Concomitant use of fluconazole and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fluoxetine: (Moderate) Concomitant use of fluoxetine and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fluphenazine: (Major) Use fluphenazine with apomorphine with caution; avoid use if possible due to an increased risk for QT prolongation and sedation. Also, the effectiveness of either agent may be decreased due to opposing effects on dopamine; consider if an atypical antipsychotic would be a suitable alternative to fluphenazine. Additive CNS depression is also possible. Limited data indicate that QT prolongation is possible with fluphenazine administration. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Flurazepam: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and benzodiazepines could result in additive depressant effects.
Fluvoxamine: (Moderate) Exercise caution when administering apomorphine concomitantly with fluvoxamine since concurrent use may increase the risk of QT prolongation. QT prolongation and torsade de pointes (TdP) have been reported during postmarketing use of fluvoxamine. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as apomorphine. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
Fostemsavir: (Moderate) Use apomorphine and fostemsavir together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, 4 times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and apomorphine. Concomitant use of gabapentin with apomorphine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as apomorphine, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Gemifloxacin: (Moderate) Exercise caution when administering apomorphine concomitantly with gemifloxacin sincce concurrent use may increase the risk of QT prolongation. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and apomorphine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes. If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Gilteritinib: (Moderate) Use caution and monitor for evidence of QT prolongation if concurrent use of gilteritinib and apomorphine is necessary since concurrent use may increase the risk of QT prolongation. Gilteritinib has been associated with QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Glasdegib: (Major) Avoid coadministration of glasdegib with apomorphine due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Goserelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving apomorphine. Androgen deprivation therapy may prolong the QT/QTc interval. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Granisetron: (Contraindicated) The concurrent use of apomorphine and serotonin-receptor antagonists is contraindicated due to the possibility of an excessive lowering of blood pressure and unconsciousness. Additionally, additive QT prolongation is possible during coadministration of apomorphine with dolasetron, granisetron, and ondansetron.
Guaifenesin; Hydrocodone: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking apomorphine. Limit the use of opioid pain medications with entacapone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Halogenated Anesthetics: (Major) Use apomorphine and halogenated anesthetics together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Halogenated anesthetics can prolong the QT interval. In addition, concomitant administration of apomorphine and halogenated anesthetics could also result in additive depressant effects.
Haloperidol: (Major) Avoid use of haloperidol with apomorphine when possible. Concurrent use may result in additive CNS depression and QT prolongation. The effectiveness of either agent may be decreased due to opposing effects on dopamine; consider if an atypical antipsychotic would be a suitable alternative to haloperidol. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. In general, atypical antipsychotics are less likely to interfere with Parkinson's disease treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, sedation, fast, irregular heartbeat, and diminished effectiveness of either agent if coadministration cannot be avoided.
Histrelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving apomorphine since concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking apomorphine. Limit the use of opioid pain medications with entacapone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Hydrocodone: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking apomorphine. Limit the use of opioid pain medications with entacapone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking apomorphine. Limit the use of opioid pain medications with entacapone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking apomorphine. Limit the use of opioid pain medications with entacapone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Hydromorphone: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Hydroxychloroquine: (Major) Avoid coadministration of apomorphine and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Hydroxyzine: (Moderate) Caution is recommended if hydroxyzine is administered with apomorphine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including apomorphine. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Ibuprofen; Oxycodone: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Ibutilide: (Major) Use apomorphine and ibutilide together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Iloperidone: (Major) Avoid use of apomorphine and iloperidone together if possible due to an additive risk for QT prolongation and sedation. Apomorphine and iloperidone may decrease the effectiveness of each other due to opposing effects on dopamine. Additive CNS effects are also possible. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Iloperidone has also been associated with QT prolongation. In general, atypical antipsychotics are less likely to interfere with Parkinson's disease treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, sedation, fast, irregular heartbeat, and diminished effectiveness of either agent if coadministration cannot be avoided.
Imipramine: (Moderate) Use apomorphine and tricyclic antidepressants together with caution due to the risk of additive QT prolongation. Tricyclic antidepressants have been associated with QT prolongation, primarily in overdosage or when excessive plasma concentrations are encountered. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Additive sedation is also possible during combined use of these agents.
Indapamide: (Moderate) Use of indapamide and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with apomorphine due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Isoflurane: (Major) Use apomorphine and halogenated anesthetics together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Halogenated anesthetics can prolong the QT interval. In addition, concomitant administration of apomorphine and halogenated anesthetics could also result in additive depressant effects.
Itraconazole: (Moderate) Exercise caution when administering apomorphine concomitantly with itraconazole since concurrent use may increase the risk of QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Itraconazole has been associated with prolongation of the QT interval.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with apomorphine due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Ketamine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and apomorphine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin with apomorphine when possible. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Lapatinib: (Moderate) Monitor for evidence of QT prolongation if lapatinib is administered with apomorphine since concurrent use may increase the risk of QT prolongation. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and apomorphine. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as apomorphine, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Lefamulin: (Major) Avoid coadministration of lefamulin with apomorphine since concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and apomorphine. Dosage adjustments of lemborexant and apomorphine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with apomorphine due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Leuprolide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving apomorphine. Androgen deprivation therapy may prolong the QT/QTc interval. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Leuprolide; Norethindrone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving apomorphine. Androgen deprivation therapy may prolong the QT/QTc interval. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with apomorphine should generally be avoided because of the possibility of additive sedative effects. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Levofloxacin: (Moderate) Concomitant use of levofloxacin and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and apomorphine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Levorphanol: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Reduce the initial dose of levorphanol by approximately 50% or more. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Lithium: (Moderate) Concomitant use of lithium and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lofexidine: (Major) Monitor the ECG if lofexidine is coadministered with apomorphine due to the potential for additive QT prolongation. Additionally, both drugs are associated with orthostatic hypotension and sedation and careful monitoring for these adverse effects is recommended. Lofexidine prolongs the QT interval, and torsade de pointes (TdP) has been reported during postmarketing use. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Loop diuretics: (Moderate) Use of loop diuretics and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Loperamide: (Moderate) Concomitant use of loperamide and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Loperamide; Simethicone: (Moderate) Concomitant use of loperamide and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir; ritonavir with apomorphine due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Lorazepam: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and benzodiazepines could result in additive depressant effects.
Loxapine: (Major) Due to opposing effects on central dopaminergic activity, loxapine and dopamine agonists may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to loxapine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Lumateperone: (Moderate) Due to mutually opposing effects on dopamine, lumateperone and apomorphine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics, such as lumateperone, are less likely to interfere with apomorphine than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of either agent during coadministration.
Lurasidone: (Moderate) Due to mutually opposing effects on dopamine, lurasidone and apomorphine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with Parkinson's disease treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, sedation, and diminished effectiveness of either agent during coadministration.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as apomorphine. Use of these drugs together may increase the risk of developing torsade de pointes. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the QTc interval. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Maprotiline: (Major) Exercise caution when administering apomorphine concomitantly with maprotiline as concurrent use may increase the risk of QT prolongation and CNS depression. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Dopaminergic agents like apomorphine have been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Mecamylamine: (Moderate) Patients receiving apomorphine may experience orthostatic hypotension, hypotension, and/or syncope. Extreme caution should be exercised if apomorphine is used concurrently with antihypertensive agents, or vasodilators such as nitrates.
Meclizine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and meclizine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Mefloquine: (Moderate) Exercise caution when administering apomorphine concomitantly with mefloquine due to the potential for additive QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Meperidine: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Metaxalone: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
Methadone: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering methadone with apomorphine. The need to coadminister these drugs should be done with extreme caution and a careful assessment of treatment risks versus benefits. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Methadone is associated with an increased risk for QT prolongation and TdP, especially at higher doses (greater than 200 mg/day but averaging approximately 400 mg/day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Additionally, apomorphine and methadone can cause significant somnolence which may be additive. A dose reduction of one or both drugs may be warranted.
Methocarbamol: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
Methylphenidate Derivatives: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as pergolide, pramipexole, apomorphine, and ropinirole. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Metoclopramide: (Moderate) Agents with dopamine antagonist properties, like metoclopramide, may decrease the effectiveness of dopamine agonists. These agents can cause abrupt and severe worsening of Parkinson's disease or restless leg syndrome (RLS) symptoms. Metoclopramide should be avoided, if possible, in patients treated with dopamine agonists for Parkinson's disease. If not avoidable, monitor for reduced efficacy of the dopamine agonist. Additive somnolence may also be possible.
Metronidazole: (Moderate) Concomitant use of metronidazole and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Midazolam: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and benzodiazepines could result in additive depressant effects.
Midostaurin: (Major) The concomitant use of midostaurin and apomorphine may lead to additive QT interval prolongation. If these drugs are used together, consider obtaining electrocardiograms to monitor the QT interval. In clinical trials, QT prolongation was reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Mifepristone: (Major) Concomitant use of apomorphine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mirtazapine: (Major) Exercise caution when administering apomorphine concomitantly with mirtazapine as concurrent use may increase the risk of QT prolongation and CNS depression. Mirtazapine has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported postmarketing, primarily in overdose or in patients with other risk factors for QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Additive sedation may also occur.
Mobocertinib: (Major) Concomitant use of mobocertinib and apomorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Molindone: (Major) Due to opposing effects on central dopaminergic activity, molindone and dopamine agonists may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to molindone. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Morphine: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Morphine; Naltrexone: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Moxifloxacin: (Major) Concurrent use of apomorphine and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Moxifloxacin has been associated with prolongation of the QT interval. Additionally, postmarketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded.
Nabilone: (Moderate) Concomitant use of nabilone with other CNS depressants can potentiate the effects of nabilone on respiratory depression. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Nefazodone: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants, including nefazodone, could result in additive depressant effects. Careful monitoring is recommended during combined use of a CNS depressant and apomorphine. A dose reduction of one or both drugs may be warranted.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and other drugs with a known potential to prolong the QT interval such as apomorphine; significant prolongation of the QT interval may occur. Sudden death and QT interval prolongation have been reported in patients who received nilotinib therapy. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Nitrates: (Major) Coadministration of apomorphine and nitrates can cause large decreases in blood pressure. The effect is especially of concern with use of sublingual nitroglycerin products. Instruct patients to lie down before taking a sublingual nitroglycerin dose and to remain supine for at least 45 minutes after to reduce orthostatic risk. In one evaluation, the largest mean decreases in standing systolic and diastolic blood pressure during use of apomorphine and sublingual nitroglycerin were 14.3 mmHg and 13.5 mmHg, respectively. The largest recorded decreases in standing systolic and diastolic blood pressures were 65 mmHg and 43 mmHg during use of apomorphine and sublingual nitroglycerin together.
Nortriptyline: (Moderate) Use apomorphine and tricyclic antidepressants together with caution due to the risk of additive QT prolongation. Tricyclic antidepressants have been associated with QT prolongation, primarily in overdosage or when excessive plasma concentrations are encountered. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Additive sedation is also possible during combined use of these agents.
Ofloxacin: (Moderate) Concomitant use of ofloxacin and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine: (Moderate) Coadministration of apomorphine and olanzapine may increase the risk for QT prolongation or sedation. Apomorphine and olanzapine may decrease the effectiveness of each other due to opposing effects on dopamine. Additive CNS effects are also possible. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. In general, atypical antipsychotics are less likely to interfere with Parkinson's disease treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, sedation, fast, irregular heartbeat, and diminished effectiveness of either agent during coadministration.
Olanzapine; Fluoxetine: (Moderate) Coadministration of apomorphine and olanzapine may increase the risk for QT prolongation or sedation. Apomorphine and olanzapine may decrease the effectiveness of each other due to opposing effects on dopamine. Additive CNS effects are also possible. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. In general, atypical antipsychotics are less likely to interfere with Parkinson's disease treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, sedation, fast, irregular heartbeat, and diminished effectiveness of either agent during coadministration. (Moderate) Concomitant use of fluoxetine and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine; Samidorphan: (Moderate) Coadministration of apomorphine and olanzapine may increase the risk for QT prolongation or sedation. Apomorphine and olanzapine may decrease the effectiveness of each other due to opposing effects on dopamine. Additive CNS effects are also possible. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. In general, atypical antipsychotics are less likely to interfere with Parkinson's disease treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, sedation, fast, irregular heartbeat, and diminished effectiveness of either agent during coadministration.
Oliceridine: (Major) Concomitant use of oliceridine with apomorphine may cause excessive sedation and somnolence. Limit the use of oliceridine with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Ondansetron: (Contraindicated) The concurrent use of apomorphine and serotonin-receptor antagonists is contraindicated due to the possibility of an excessive lowering of blood pressure and unconsciousness. Additionally, additive QT prolongation is possible during coadministration of apomorphine with dolasetron, granisetron, and ondansetron.
Orphenadrine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
Osilodrostat: (Moderate) Monitor ECGs in patients receiving osilodrostat with apomorphine since concurrent use may increase the risk of QT prolongation. Osilodrostat is associated with dose-dependent QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Osimertinib: (Major) Avoid coadministration of apomorphine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Oxaliplatin: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and apomorphine concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Oxazepam: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and benzodiazepines could result in additive depressant effects.
Oxycodone: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Oxymorphone: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with entacapone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Reduce the initial oxymorphone dosage by 1/3 to 1/2. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking apomorphine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Pacritinib: (Major) Concomitant use of pacritinib and apomorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Moderate) Coadministration of apomorphine and paliperidone may increase the risk for QT prolongation or sedation. Apomorphine and paliperidone may decrease the effectiveness of each other due to opposing effects on dopamine. Additive CNS effects are also possible. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. In general, atypical antipsychotics are less likely to interfere with Parkinson's disease treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, sedation, fast, irregular heartbeat, and diminished effectiveness of either agent during coadministration.
Palonosetron: (Contraindicated) The concurrent use of apomorphine and serotonin-receptor antagonists is contraindicated due to the possibility of an excessive lowering of blood pressure and unconsciousness. Additionally, additive QT prolongation is possible during coadministration of apomorphine with dolasetron, granisetron, and ondansetron.
Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to 480 milliseconds or more during therapy; permanently discontinue if QT prolongation does not resolve. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Pasireotide: (Moderate) Use apomorphine and pasireotide together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Pazopanib: (Major) Concurrent use of pazopanib and apomorphine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be continued, closely monitor the patient for QT interval prolongation. Pazopanib has been reported to prolong the QT interval. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Pentamidine: (Major) Use apomorphine and pentamidine together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Systemic pentamidine has been associated with QT prolongation.
Perphenazine: (Major) Use perphenazine with apomorphine with caution; avoid use if possible due to an increased risk for QT prolongation and sedation. Also, the effectiveness of either agent may be decreased due to opposing effects on dopamine; consider if an atypical antipsychotic would be a suitable alternative to perphenazine. Additive CNS depression is also possible. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Perphenazine is associated with a possible risk for QT prolongation.
Perphenazine; Amitriptyline: (Major) Use perphenazine with apomorphine with caution; avoid use if possible due to an increased risk for QT prolongation and sedation. Also, the effectiveness of either agent may be decreased due to opposing effects on dopamine; consider if an atypical antipsychotic would be a suitable alternative to perphenazine. Additive CNS depression is also possible. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Perphenazine is associated with a possible risk for QT prolongation. (Moderate) Use apomorphine and tricyclic antidepressants together with caution due to the risk of additive QT prolongation. Tricyclic antidepressants have been associated with QT prolongation, primarily in overdosage or when excessive plasma concentrations are encountered. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Additive sedation is also possible during combined use of these agents.
Phenoxybenzamine: (Moderate) Use of phenoxybenzamine and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Phentolamine: (Moderate) Use of phentolamine and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as apomorphine. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of apomorphine with pimozide is contraindicated. Apomorphine is also associated with QT prolongation. In addition, the use of pimozide may counteract the effectiveness of apomorphine due to its dopamine antagonist actions. Both agents also cause sedation.
Pitolisant: (Major) Avoid coadministration of pitolisant with apomorphine since concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking apomorphine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Posaconazole: (Moderate) Exercise caution when administering apomorphine concomitantly with posaconazole since concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Potassium-sparing diuretics: (Moderate) Use of potassium-sparing diuretics and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Pramipexole: (Moderate) Concomitant administration of apomorphine and CNS depressants, such as pramipexole, could result in additive depressant effects. Careful monitoring is recommended during combined use of pramipexolet and apomorphine. A dose reduction of one or both drugs may be warranted.
Prazosin: (Moderate) Use of prazosin and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and apomorphine. Concomitant use of pregabalin with apomorphine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as apomorphine, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Primaquine: (Moderate) Exercise caution when administering apomorphine concomitantly with primaquine since concurrent use may increase the risk of QT prolongation. Primaquine has the potential to prolong the QT interval. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Procainamide: (Major) Use apomorphine and procainamide together with caution due to the risk of additive QT prolongation. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Prochlorperazine: (Major) Use prochlorperazine with apomorphine with caution; avoid use if possible due to an increased risk for QT prolongation and sedation. Also, the effectiveness of either agent may be decreased due to opposing effects on dopamine; consider if an atypical antipsychotic would be a suitable alternative to prochlorperazine. Additive CNS depression is also possible. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Many phenothiazine drugs are associated with a possible risk for QT prolongation.
Promethazine: (Moderate) Use promethazine with apomorphine with caution; avoid use if possible due to an increased risk for QT prolongation and sedation. Promethazine and apomorphine may reduce the effectiveness of each other through opposing effects on dopamine. Apomorphine causes considerable somnolence, and concomitant administration of apomorphine and CNS depressants like promethazine could result in additive CNS effects. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Promethazine is associated with a possible risk for QT prolongation.
Promethazine; Dextromethorphan: (Moderate) Use promethazine with apomorphine with caution; avoid use if possible due to an increased risk for QT prolongation and sedation. Promethazine and apomorphine may reduce the effectiveness of each other through opposing effects on dopamine. Apomorphine causes considerable somnolence, and concomitant administration of apomorphine and CNS depressants like promethazine could result in additive CNS effects. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Promethazine is associated with a possible risk for QT prolongation.
Promethazine; Phenylephrine: (Moderate) Use promethazine with apomorphine with caution; avoid use if possible due to an increased risk for QT prolongation and sedation. Promethazine and apomorphine may reduce the effectiveness of each other through opposing effects on dopamine. Apomorphine causes considerable somnolence, and concomitant administration of apomorphine and CNS depressants like promethazine could result in additive CNS effects. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Promethazine is associated with a possible risk for QT prolongation.
Propafenone: (Major) Concomitant use of propafenone and apomorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Propofol: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
Protriptyline: (Moderate) Use apomorphine and tricyclic antidepressants together with caution due to the risk of additive QT prolongation. Tricyclic antidepressants have been associated with QT prolongation, primarily in overdosage or when excessive plasma concentrations are encountered. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Additive sedation is also possible during combined use of these agents.
Pseudoephedrine; Triprolidine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and carbinoxamine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Quazepam: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and benzodiazepines could result in additive depressant effects.
Quetiapine: (Major) Avoid use of quetiapine and apomorphine if possible due to an increased risk for QT prolongation and sedation. Also, quetiapine and apomorphine may reduce the effectiveness of each other through opposing effects on dopamine. Additive CNS effects are also possible. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. In general, atypical antipsychotics are less likely to interfere with Parkinson's disease treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, sedation, fast, irregular heartbeat, and diminished effectiveness of either agent if coadministration cannot be avoided.
Quinidine: (Major) Use apomorphine and quinidine together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Quinidine administration is associated with QT prolongation and torsades de pointes.
Quinine: (Major) Concurrent use of quinine and apomorphine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Quizartinib: (Major) Concomitant use of quizartinib and apomorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ranolazine: (Moderate) Exercise caution when administering apomorphine concomitantly with ranolazine since concurrent use may increase the risk of QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval.
Relugolix: (Moderate) Use apomorphine and relugolix together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Use apomorphine and relugolix together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Remifentanil: (Major) Apomorphine may cause additive sedation or hypotension with remifentanil. Monitor patients receiving remifentanil with other CNS depressants for hypotension and prolonged respiratory depression and sedation. In such cases of combined treatment, a dose reduction of one or both agents may be necessary.
Remimazolam: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and benzodiazepines could result in additive depressant effects.
Ribociclib: (Major) Avoid coadministration of ribociclib with apomorphine due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with apomorphine due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Rilpivirine: (Moderate) Exercise caution when administering apomorphine concomitantly with rilpivirine since concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Risperidone: (Moderate) Use risperidone and apomorphine together with caution due to a potential for additive QT prolongation and sedation. Also, risperidone and apomorphine may reduce the effectiveness of each other due to opposing effects on dopamine. Additive CNS effects are also possible. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. In general, atypical antipsychotics are less likely to interfere with Parkinson's disease treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, sedation, fast, irregular heartbeat, and diminished effectiveness of either agent during coadministration.
Romidepsin: (Moderate) Use apomorphine and romidepsin together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Consider monitoring electrolytes and ECGs at baseline and periodically during treatment if romidepsin is administered with apomorphine. Romidepsin has been reported to prolong the QT interval.
Ropinirole: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants, such as ropinirole, could result in additive depressant effects. Careful monitoring is recommended during combined use of a CNS depressant and apomorphine. A dose reduction of one or both drugs may be warranted.
Saquinavir: (Major) Concurrent use of saquinavir and apomorphine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as TdP. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations.
Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with apomorphine is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Serotonin-Receptor Antagonists: (Contraindicated) The concurrent use of apomorphine and serotonin-receptor antagonists is contraindicated due to the possibility of an excessive lowering of blood pressure and unconsciousness. Additionally, additive QT prolongation is possible during coadministration of apomorphine with dolasetron, granisetron, and ondansetron.
Sertraline: (Moderate) Concomitant use of sertraline and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sevoflurane: (Major) Use apomorphine and halogenated anesthetics together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Halogenated anesthetics can prolong the QT interval. In addition, concomitant administration of apomorphine and halogenated anesthetics could also result in additive depressant effects.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving apomorphine due to the potential for QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study.
Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Solifenacin: (Moderate) Apomorphine and solifenacin should be coadministered cautiously and with close monitoring since concurrent use may increase the risk of QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality has not been established.
Solriamfetol: (Moderate) Monitor for dopamine-mediated effects including nausea, vomiting, dizziness, tremor, and changes in moods or behaviors if solriamfetol, a central dopamine and norepinephrine reuptake inhibitor, is administered with other dopaminergic drugs, such as apomorphine. Caution is recommended since this combination has not been evaluated.
Sorafenib: (Major) Avoid coadministration of sorafenib with apomorphine due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Sorafenib is also associated with QTc prolongation.
Sotalol: (Major) Concomitant use of sotalol and apomorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and apomorphine. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Major) Apomorphine may cause additive sedation or hypotension with sufentanil. Monitor patients receiving sufentanil with other CNS depressants for hypotension and prolonged respiratory depression and sedation. In such cases of combined treatment, a dose reduction of one or both agents may be necessary.
Sunitinib: (Moderate) Use apomorphine and sunitinib together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Sunitinib can prolong the QT interval.
Tacrolimus: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with apomorphine. Tacrolimus may prolong the QT interval and cause torsade de pointes. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Tamoxifen: (Moderate) Concomitant use of tamoxifen and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tapentadol: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Telavancin: (Moderate) Exercise caution when administering apomorphine concomitantly with telavancin since concurrent use may increase the risk of QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Telavancin has been associated with QT prolongation.
Temazepam: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and benzodiazepines could result in additive depressant effects.
Terazosin: (Moderate) Use of terazosin and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Tetrabenazine: (Major) Exercise caution when using apomorphine with tetrabenazine due to an increased risk for QT prolongation and CNS depression. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Tetrabenazine causes a small increase in the corrected QT interval (QTc) and is associated with a possible risk for torsade de pointes (TdP). Sedation is the most common dose-limiting adverse reaction of tetrabenazine, and apomorphine also causes significant somnolence.
Thiazide diuretics: (Moderate) Use of thiazide diuretics and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Thioridazine: (Contraindicated) Thioridazine is considered contraindicated for use along with apomorphine which, when combined with thioridazine, may prolong the QT interval and increase the risk of torsade de pointes (TdP), and/or cause orthostatic hypotension. Thioridazine is associated with a well-established risk of QT prolongation and TdP. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. In addition, thioridazine and apomorphine may reduce the effects of each other through opposing effects on dopamine.
Thiothixene: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and dopamine agonists may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic instead of thiothixene, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Tolterodine: (Moderate) Exercise caution when administering apomorphine concomitantly with tolterodine since concurrent use may increase the risk of QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
Toremifene: (Major) Avoid coadministration of apomorphine with toremifene if possible due to the risk of additive QT prolongation. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene.
Tramadol: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Tramadol; Acetaminophen: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Trazodone: (Major) Apomorphine should be avoided in combination with trazodone due to the potential for additive QT prolongation and sedation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are postmarketing reports of torsade de pointes (TdP). Apomorphine also causes considerable somnolence, and concomitant administration of apomorphine and CNS depressants like trazodone could result in additive CNS effects.
Triazolam: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and benzodiazepines could result in additive depressant effects.
Triclabendazole: (Moderate) Concomitant use of triclabendazole and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tricyclic antidepressants: (Moderate) Use apomorphine and tricyclic antidepressants together with caution due to the risk of additive QT prolongation. Tricyclic antidepressants have been associated with QT prolongation, primarily in overdosage or when excessive plasma concentrations are encountered. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Additive sedation is also possible during combined use of these agents.
Trifluoperazine: (Major) Use trifluoperazine with apomorphine with caution; avoid use if possible due to an increased risk for QT prolongation and sedation. Also, the effectiveness of either agent may be decreased due to opposing effects on dopamine; consider if an atypical antipsychotic would be a suitable alternative to trifluoperazine. Additive CNS depression is also possible. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Many phenothiazine antipsychotics are associated with a possible risk for QT prolongation.
Trimethobenzamide: (Moderate) Because apomorphine may cause somnolence or dizziness, monitor for additive sedation or dizziness when trimethobenzamide or other sedating anti-emetics are used with apomorphine.
Trimipramine: (Moderate) Use apomorphine and tricyclic antidepressants together with caution due to the risk of additive QT prolongation. Tricyclic antidepressants have been associated with QT prolongation, primarily in overdosage or when excessive plasma concentrations are encountered. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Additive sedation is also possible during combined use of these agents.
Triprolidine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and carbinoxamine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Triptorelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving apomorphine. Androgen deprivation therapy may prolong the QT/QTc interval. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Vandetanib: (Major) Avoid coadministration of vandetanib with apomorphine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Vardenafil: (Moderate) Concomitant use of vardenafil and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vasodilators: (Moderate) Concurrent use of apomorphine and vasodilators can cause greater decreases in blood pressure than use of apomorphine alone. Patients receiving a combination of apomorphine and vasodilators should be closely monitored for hypotension and orthostasis.
Vemurafenib: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering vemurafenib with apomorphine. If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Vemurafenib has been associated with QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Venlafaxine: (Moderate) Concomitant use of venlafaxine and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Voclosporin: (Moderate) Concomitant use of voclosporin and apomorphine may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin with apomorphine when possible. Clarithromycin is associated with an established risk for QT prolongation and torsade de pointes (TdP). Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Voriconazole: (Moderate) Exercise caution when administering apomorphine concomitantly with voriconazole since concurrent use may increase the risk of QT prolongation. Voriconazole has been associated with QT prolongation and rare cases of torsade de pointes. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Vorinostat: (Moderate) Exercise caution when administering apomorphine concomitantly with vorinostat since concurrent use may increase the risk of QT prolongation. Vorinostat therapy is associated with a risk of QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Ziprasidone: (Major) Avoid use of apomorphine and ziprasidone together if possible due to a risk for additive QT prolongation and sedation. Also, apomorphine and ziprasidone can reduce the effectiveness of each other through opposing effects on dopamine. Addtive CNS effects are also possible. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. In general, atypical antipsychotics are less likely to interfere with Parkinson's disease treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, sedation, fast, irregular heartbeat, and diminished effectiveness of either agent if coadministration cannot be avoided.

Apokyn/Apomorphine/Apomorphine Hydrochloride Subcutaneous Inj Sol: 1mL, 10mg
KYNMOBI Oral Film: 10-15-20-25-30mg
KYNMOBI Sublingual Film: 10mg, 15mg, 20mg, 25mg, 30mg, 10-15-20-25-30mg

Adults

0.6 mL (6 mg) per single subcutaneous injection and 5 injections/day not to exceed 2 mL/day (20 mg)/day subcutaneously; for sublingual dosage form: 30 mg/dose SL and no more than 5 doses/day SL.

Geriatric

0.6 mL (6 mg) per single subcutaneous injection and 5 injections/day not to exceed 2 mL/day (20 mg)/day subcutaneously; for sublingual dosage form: 30 mg/dose SL and no more than 5 doses/day SL.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Apomorphine has structural similarities to the neurotransmitter dopamine that are thought to contribute to its central dopamine receptor agonist properties. Apomorphine exhibits a high affinity for dopamine D4 receptors, a moderate affinity for dopamine D2, D3, and D5 receptors, and a low affinity for D1 receptors. Apomorphine may be a partial agonist at D1 receptors; however, further studies are needed to confirm this effect. Although the exact mechanism by which apomorphine exerts its therapeutic effects in Parkinson's disease is unknown, it is thought to occur via activation at postsynaptic D2 receptors in the caudate nucleus and putamen. Apomorphine has a moderate affinity for alpha-1D, alpha-2B, and alpha-2C adrenergic receptors, and a low affinity for the serotonin receptors 5-HT1A, 5-HT2A, 5-HT2B, and 5-HT2C. Stimulation of the chemoreceptor trigger zone (CTZ) by the drug produces potent emetic actions. Apomorphine is a morphine derivative, but generally does not possess any narcotic effects, with the exception of emesis induction, CNS depression, and respiratory depression.

Apomorphine is administered by subcutaneous injection or sublingual film. A high first-pass metabolism prohibits the use of an oral formulation. Apomorphine has a large volume of distribution and is 85% to 90% bound to plasma proteins, predominantly to albumin. Maximum concentrations in cerebrospinal fluid (CSF) are less than 10% of maximum plasma concentrations and occur 10 minutes to 20 minutes after maximum plasma concentrations are achieved from subcutaneous dosing. Metabolism is thought to occur in the liver through several pathways including glucuronidation, sulfation, and N-demethylation. Apomorphine does not appear to be significantly metabolized by catechol-O-methyl transferase (COMT). The primary metabolite, apomorphine sulfate, is not pharmacologically active. N-demethylation produces norapomorphine. This metabolite is thought to possess some pharmacologic activity, but it has a lower affinity for dopamine receptors than the parent compound. Several CYP450 isoenzymes are thought to be involved in the demethylation of apomorphine including CYP2B6, CYP3A4/5, and CYP2C8, but these appear to have a very minor role in the metabolism of the drug according to in vitro studies. Subcutaneous apomorphine has a mean elimination half-life of about 40 minutes (range: 30 to 60 minutes). Sublingual apomorphine has a mean elimination half-life of about 1.7 hours (range: 0.8 hours to 3 hours). The apparent clearance of apomorphine does not appear to be influenced by the duration of Parkinson's disease, levodopa dose, use of antiemetic, or duration of therapy.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None
CYP2B6, CYP3A4/5, and CYP2C8 are thought to be involved in the demethylation of apomorphine, but these isoenzymes appear to have a very minor role in the metabolism of the drug. In vitro studies indicate that apomorphine is unlikely to act as a CYP inhibitor or inducer.

Subcutaneous Route

The absorption of apomorphine after subcutaneous injection is dependent on many variables such as location of injection, body temperature, and percentage of body fat. Abdominal injections result in faster absorption than injections into the thigh, and lowering the temperature of the injection site slows absorption. Improvement in Parkinson's symptoms become evident within about 7 to 14 minutes following a subcutaneous injection, with a duration of action up to 2 hours. Onset of emesis occurs within 3 to 10 minutes of a subcutaneous dose, with a duration of 60 minutes.

Inhalation Route

Intranasal Administration
Alternative formulations (e.g., intranasal inhalation) of apomorphine have been investigated as potential delivery systems but are not FDA-approved. Optimal dosages for intranasal apomorphine range from 2 to 5 mg per inhalation with benefit seen at 7.5 minutes and a duration of action ranging from 45 to 55 minutes. Side effects have included nasal irritation, vestibulitis, dyskinesias, yawning, and nausea.

Other Route(s)

Sublingual Administration (e.g., Kynmobi sublingual film)
Following sublingual administration of 15 mg of apomorphine, the time to maximum concentration (Tmax) ranged from 0.5 to 1 hour. Apomorphine exhibits less than a dose-proportional increase in exposures over a dose range of 10 mg to 35 mg (1.2 times the highest recommended dosage) following a single sublingual dose of apomorphine in patients with Parkinson's disease.
 
Rectal Administration
Alternative formulations (e.g., rectal) of apomorphine have been investigated as potential delivery systems, but are not FDA-approved. Rectal administration of apomorphine has been evaluated in limited, usually post-operative settings. Administration of a 200 mg apomorphine rectal suppository resulted in an average time to benefit of 32 minutes with an average duration of action of 195 minutes. Sedation, nausea, and faintness were reported as side effects.

Pregnancy

There are no adequate data on the developmental risks associated with the use of apomorphine during human pregnancy. Apomorphine has been administered to a limited number of pregnant women prior to undergoing Caesarean section. Infant Apgar scores were similar between the 2 groups and depressant effects were not observed in the apomorphine infant group; however, the women did not receive apomorphine chronically and also received the drug close to obstetric delivery. In animal reproduction studies, apomorphine was associated with adverse developmental effects, an increased incidence of fetal malformations, and maternal toxicity when administered during pregnancy at clinically relevant doses.

There are no data on the presence of apomorphine in human milk, the effects of apomorphine on the breastfed infant, or the effects of apomorphine on milk production. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for apomorphine and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.