apomorphine (Rx)

Brand and Other Names:Apokyn, Kynmobi

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

solution for SC injection

  • 10mg/mL (30mg/3mL pen injector) (Apokyn, generic)

SL film (Kynmobi)

  • 10mg
  • 15mg
  • 20mg
  • 25mg
  • 30mg

Parkinson Disease

Indicated for acute, intermittent treatment of hypomobility, "off" episodes (end-of-dose wearing "off" and unpredictable "on-off" episodes) associated with advanced Parkinson disease

Subcutaneous (Apokyn)

  • Initial: 2 mg (0.2 mL) SC PRN
  • Also see Administration for details regarding test dose
  • Titrate on the basis of effectiveness and tolerance; not to exceed 6 mg (0.6 mL)/dose
  • Average frequency of dosing in clinical trials was TID
  • Limited experience with single doses >6 mg, dosing >5 times per day, or with total daily doses >20 mg

Sublingual (Kynmobi)

  • Initial: 10 mg SL PRN; not to exceed 5 doses/day
  • Separate doses by at least 2 hr; if a single dose is ineffective for a particular “off” episode, a second dose should not be given for that “off” episode
  • Maximum single dose: 30 mg

Premedication

  • High incidence of nausea and vomiting with treatment; initiate an antiemetic (eg, trimethobenzamide 300 mg TID) 3 days prior to the initial apomorphine dose
  • Treatment with trimethobenzamide should only be continued as long as necessary to control nausea and vomiting, and generally no longer than 2 months after initiation of treatment
  • Trimethobenzamide increases the incidence of somnolence, dizziness, and falls
  • Contraindicated with 5HT3 antagonist antiemetics (eg, ondansetron, granisetron, dolasetron, palonosetron) owing to profound hypotension and loss of consciousness when coadministered

Dosage Modifications

Renal impairment

  • Mild-to-moderate: Reduce test dose and starting dose to 1 mg (0.1 mL); peak plasma concentration and AUC increased in these patients
  • Severe: Not studied

Hepatic impairment

  • Mild–to-moderate: Use caution; peak plasma concentration and AUC increased in these patients
  • Severe: Not studied

Vegetative State (Orphan)

Treatment of patients in a vegetative state or minimally conscious state for up to 12 months following a severe traumatic brain injury

Orphan indication sponsor

  • NeuroHealing Pharmaceuticals, Inc; 50 Undine Road; Newton, MA 02135

Acute Myeloid Leukemia (Orphan)

Orphan designation for treatment of acute myeloid leukemia (AML)

Orphan sponsor

  • Leukos Biotech; Muntaner 383, 3°2°; Barcelona, Spain

Amyotrophic Lateral Sclerosis (Orphan)

Orphan designation for treatment of amyotrophic lateral sclerosis (ALS)

Orphan sponsor

  • Aclipse One Inc; 170 North Radnor Chester Road, Suite 350; Wayne, Pennsylvania 19087

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and apomorphine

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            Contraindicated (9)

            • alosetron

              apomorphine, alosetron. Mechanism: unspecified interaction mechanism. Contraindicated. Profound hypotension and loss of consciousness reported when 5HT3 antagonists are coadministered with apomorphine. .

            • cisapride

              apomorphine and cisapride both increase QTc interval. Contraindicated.

            • dolasetron

              apomorphine, dolasetron. Mechanism: unspecified interaction mechanism. Contraindicated. Profound hypotension and loss of consciousness reported when 5HT3 antagonists are coadministered with apomorphine. Additionally, dolasetron may cause additive QT prolongation with apomorphine.

              dolasetron and apomorphine both increase QTc interval. Contraindicated.

            • dronedarone

              apomorphine and dronedarone both increase QTc interval. Contraindicated.

            • granisetron

              apomorphine, granisetron. Mechanism: unspecified interaction mechanism. Contraindicated. Profound hypotension and loss of consciousness reported when 5HT3 antagonists are coadministered with apomorphine. .

            • netupitant/palonosetron

              netupitant/palonosetron, apomorphine. Mechanism: unspecified interaction mechanism. Contraindicated. Profound hypotension and loss of consciousness reported when 5HT3 antagonists are coadministered with apomorphine. .

            • ondansetron

              apomorphine, ondansetron. Mechanism: unspecified interaction mechanism. Contraindicated. Profound hypotension and loss of consciousness reported when 5HT3 antagonists are coadministered with apomorphine. Additionally, ondansetron may cause additive QT prolongation with apomorphine.

            • palonosetron

              apomorphine, palonosetron. Mechanism: unspecified interaction mechanism. Contraindicated. Profound hypotension and loss of consciousness reported when 5HT3 antagonists are coadministered with apomorphine. .

            • thioridazine

              apomorphine and thioridazine both increase QTc interval. Contraindicated.

            Serious - Use Alternative (94)

            • adagrasib

              adagrasib, apomorphine. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Each drug prolongs the QTc interval, which may increased the risk of Torsade de pointes, other serious arryhthmias, and sudden death. If coadministration unavoidable, more frequent monitoring is recommended for such patients.

            • amiodarone

              apomorphine and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.

            • amisulpride

              amisulpride, apomorphine. Either decreases effects of the other by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid use of amisulpride, a dopamine receptor antagonist, with dopamine agonists.

              apomorphine and amisulpride both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.

            • anagrelide

              apomorphine and anagrelide both increase QTc interval. Avoid or Use Alternate Drug.

            • aripiprazole

              aripiprazole decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • arsenic trioxide

              apomorphine and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.

            • artemether

              artemether and apomorphine both increase QTc interval. Avoid or Use Alternate Drug.

            • artemether/lumefantrine

              apomorphine and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

            • asenapine

              apomorphine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

            • asenapine transdermal

              asenapine transdermal and apomorphine both increase QTc interval. Avoid or Use Alternate Drug.

            • buprenorphine

              apomorphine and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.

            • buprenorphine buccal

              buprenorphine buccal and apomorphine both increase QTc interval. Avoid or Use Alternate Drug.

            • buprenorphine subdermal implant

              buprenorphine subdermal implant and apomorphine both increase QTc interval. Avoid or Use Alternate Drug.

            • buprenorphine transdermal

              buprenorphine transdermal and apomorphine both increase QTc interval. Avoid or Use Alternate Drug.

            • buprenorphine, long-acting injection

              buprenorphine, long-acting injection and apomorphine both increase QTc interval. Avoid or Use Alternate Drug.

            • calcium/magnesium/potassium/sodium oxybates

              apomorphine, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • ceritinib

              ceritinib and apomorphine both increase QTc interval. Avoid or Use Alternate Drug.

            • chlorpromazine

              chlorpromazine decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

              apomorphine and chlorpromazine both increase QTc interval. Avoid or Use Alternate Drug.

            • clarithromycin

              apomorphine and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.

            • clozapine

              clozapine decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • disopyramide

              apomorphine and disopyramide both increase QTc interval. Avoid or Use Alternate Drug.

            • dofetilide

              dofetilide increases toxicity of apomorphine by QTc interval. Avoid or Use Alternate Drug.

            • droperidol

              droperidol decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

              apomorphine and droperidol both increase QTc interval. Avoid or Use Alternate Drug.

            • encorafenib

              apomorphine and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • entrectinib

              apomorphine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • eribulin

              apomorphine and eribulin both increase QTc interval. Avoid or Use Alternate Drug.

            • fedratinib

              apomorphine will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

            • fexinidazole

              fexinidazole and apomorphine both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.

            • fluphenazine

              fluphenazine decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

              apomorphine and fluphenazine both increase QTc interval. Avoid or Use Alternate Drug.

            • foscarnet

              apomorphine and foscarnet both increase QTc interval. Avoid or Use Alternate Drug.

            • glasdegib

              apomorphine and glasdegib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, monitor for increased risk of QTc interval prolongation.

            • granisetron

              apomorphine and granisetron both increase QTc interval. Contraindicated.

            • haloperidol

              haloperidol decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • hydroxychloroquine sulfate

              hydroxychloroquine sulfate and apomorphine both increase QTc interval. Avoid or Use Alternate Drug.

            • ibutilide

              apomorphine and ibutilide both increase QTc interval. Avoid or Use Alternate Drug.

            • iloperidone

              iloperidone decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

              apomorphine and iloperidone both increase QTc interval. Avoid or Use Alternate Drug.

            • inotuzumab

              inotuzumab and apomorphine both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.

            • isoflurane

              isoflurane and apomorphine both increase QTc interval. Avoid or Use Alternate Drug.

            • ivosidenib

              ivosidenib and apomorphine both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of QTc prolonging drugs with ivosidenib or replace with alternate therapies. If coadministration of a QTc prolonging drug is unavoidable, monitor for increased risk of QTc interval prolongation.

            • lefamulin

              lefamulin and apomorphine both increase QTc interval. Avoid or Use Alternate Drug.

            • levofloxacin

              apomorphine and levofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

            • lofexidine

              apomorphine and lofexidine both increase QTc interval. Avoid or Use Alternate Drug.

            • lopinavir

              apomorphine and lopinavir both increase QTc interval. Avoid or Use Alternate Drug.

            • loxapine

              loxapine decreases effects of apomorphine by pharmacodynamic antagonism. Contraindicated.

            • loxapine inhaled

              loxapine inhaled decreases effects of apomorphine by pharmacodynamic antagonism. Contraindicated.

            • macimorelin

              macimorelin and apomorphine both increase QTc interval. Avoid or Use Alternate Drug. Macimorelin causes an increase of ~11 msec in the corrected QT interval. Avoid coadministration with drugs that prolong QT interval, which could increase risk for developing torsade de pointes-type ventricular tachycardia. Allow sufficient washout time of drugs that are known to prolong the QT interval before administering macimorelin.

            • maprotiline

              apomorphine and maprotiline both increase QTc interval. Avoid or Use Alternate Drug.

            • mefloquine

              apomorphine and mefloquine both increase QTc interval. Avoid or Use Alternate Drug.

            • methadone

              apomorphine and methadone both increase QTc interval. Avoid or Use Alternate Drug.

            • metoclopramide intranasal

              apomorphine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

              metoclopramide intranasal, apomorphine. dopaminergic effects. Avoid or Use Alternate Drug. Opposing effects of metoclopramide and the interacting drug on dopamine. Potential exacerbation of symptoms (eg, parkinsonian symptoms) or decreased therapeutic effects of metoclopramide.

            • midostaurin

              apomorphine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.

            • mirtazapine

              apomorphine and mirtazapine both increase QTc interval. Avoid or Use Alternate Drug.

            • moxifloxacin

              apomorphine and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

            • nilotinib

              apomorphine and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.

            • octreotide

              apomorphine and octreotide both increase QTc interval. Avoid or Use Alternate Drug.

            • ofloxacin

              apomorphine and ofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

            • olanzapine

              olanzapine decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

              apomorphine and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • olopatadine intranasal

              apomorphine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

            • oxaliplatin

              apomorphine and oxaliplatin both increase QTc interval. Avoid or Use Alternate Drug.

            • paliperidone

              paliperidone decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

              apomorphine and paliperidone both increase QTc interval. Avoid or Use Alternate Drug.

            • panobinostat

              apomorphine and panobinostat both increase QTc interval. Avoid or Use Alternate Drug. Panobinostat is known to significantly prolong QT interval. Panobinostat prescribing information states use with drugs known to prolong QTc is not recommended.

            • pazopanib

              apomorphine and pazopanib both increase QTc interval. Avoid or Use Alternate Drug.

            • pentamidine

              apomorphine and pentamidine both increase QTc interval. Avoid or Use Alternate Drug.

            • perphenazine

              perphenazine decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

              apomorphine and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.

            • pimavanserin

              apomorphine and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

            • pimozide

              pimozide decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

              apomorphine and pimozide both increase QTc interval. Contraindicated.

            • pitolisant

              apomorphine and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.

            • ponesimod

              apomorphine and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

            • procainamide

              apomorphine and procainamide both increase QTc interval. Avoid or Use Alternate Drug.

            • prochlorperazine

              prochlorperazine decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • promethazine

              promethazine decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • propafenone

              apomorphine and propafenone both increase QTc interval. Avoid or Use Alternate Drug.

            • protriptyline

              apomorphine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • quetiapine

              quetiapine decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • quinidine

              apomorphine and quinidine both increase QTc interval. Avoid or Use Alternate Drug.

            • ribociclib

              ribociclib increases toxicity of apomorphine by QTc interval. Avoid or Use Alternate Drug.

            • risperidone

              risperidone decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • saquinavir

              saquinavir, apomorphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of QT prolongation and cardiac arrhythmias.

              apomorphine and saquinavir both increase QTc interval. Avoid or Use Alternate Drug.

            • selinexor

              selinexor, apomorphine. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

            • sevoflurane

              apomorphine and sevoflurane both increase QTc interval. Avoid or Use Alternate Drug.

              sevoflurane and apomorphine both increase QTc interval. Avoid or Use Alternate Drug.

            • siponimod

              apomorphine and siponimod both increase QTc interval. Avoid or Use Alternate Drug.

            • sodium oxybate

              apomorphine, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • sotalol

              apomorphine and sotalol both increase QTc interval. Avoid or Use Alternate Drug.

            • tetrabenazine

              apomorphine and tetrabenazine both increase QTc interval. Avoid or Use Alternate Drug.

            • thioridazine

              thioridazine decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • thiothixene

              thiothixene decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • toremifene

              apomorphine and toremifene both increase QTc interval. Avoid or Use Alternate Drug. Concurrent use of toremifene with agents causing QT prolongation should be avoided. If concomitant use is required it's recommended that toremifene be interrupted. If interruption not possible, patients requiring therapy with a drug that prolongs QT should be closely monitored. ECGs should be obtained for high risk patients.

            • trazodone

              apomorphine and trazodone both increase QTc interval. Avoid or Use Alternate Drug.

            • trifluoperazine

              trifluoperazine decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • umeclidinium bromide/vilanterol inhaled

              apomorphine increases toxicity of umeclidinium bromide/vilanterol inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.

            • vandetanib

              apomorphine, vandetanib. Either increases toxicity of the other by QTc interval. Avoid or Use Alternate Drug. Avoid coadministration with drugs known to prolong QT interval; if a drug known to prolong QT interval must be used, more frequent ECG monitoring is recommended.

            • vemurafenib

              vemurafenib and apomorphine both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.

            • vilanterol/fluticasone furoate inhaled

              apomorphine increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.

            • ziprasidone

              ziprasidone decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

              apomorphine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.

            Monitor Closely (200)

            • albuterol

              albuterol and apomorphine both increase QTc interval. Use Caution/Monitor.

            • alfentanil

              alfentanil and apomorphine both increase sedation. Use Caution/Monitor.

            • alfuzosin

              apomorphine and alfuzosin both increase QTc interval. Use Caution/Monitor.

              alfuzosin and apomorphine both decrease QTc interval. Use Caution/Monitor.

            • alprazolam

              alprazolam and apomorphine both increase sedation. Use Caution/Monitor.

            • amifostine

              amifostine, apomorphine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.

            • amitriptyline

              amitriptyline and apomorphine both increase sedation. Use Caution/Monitor.

              apomorphine and amitriptyline both increase QTc interval. Use Caution/Monitor.

            • amobarbital

              amobarbital and apomorphine both increase sedation. Use Caution/Monitor.

            • amoxapine

              amoxapine and apomorphine both increase sedation. Use Caution/Monitor.

            • arformoterol

              apomorphine and arformoterol both increase QTc interval. Use Caution/Monitor.

            • aripiprazole

              aripiprazole and apomorphine both increase sedation. Use Caution/Monitor.

              aripiprazole and apomorphine both increase QTc interval. Use Caution/Monitor.

            • atomoxetine

              atomoxetine and apomorphine both increase QTc interval. Use Caution/Monitor.

            • azelastine

              azelastine and apomorphine both increase sedation. Use Caution/Monitor.

            • azithromycin

              azithromycin increases toxicity of apomorphine by QTc interval. Use Caution/Monitor.

            • baclofen

              baclofen and apomorphine both increase sedation. Use Caution/Monitor.

            • bedaquiline

              apomorphine and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closely

            • belladonna and opium

              belladonna and opium and apomorphine both increase sedation. Use Caution/Monitor.

            • benazepril

              apomorphine, benazepril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increases risk of hypotension.

            • bromocriptine

              apomorphine and bromocriptine both increase dopaminergic effects. Use Caution/Monitor. Combination may enhance efficacy. Monitor for hypotension.

            • brompheniramine

              brompheniramine and apomorphine both increase sedation. Use Caution/Monitor.

            • buprenorphine

              buprenorphine and apomorphine both increase sedation. Use Caution/Monitor.

            • buprenorphine buccal

              buprenorphine buccal and apomorphine both increase sedation. Use Caution/Monitor.

            • butabarbital

              butabarbital and apomorphine both increase sedation. Use Caution/Monitor.

            • butalbital

              butalbital and apomorphine both increase sedation. Use Caution/Monitor.

            • butorphanol

              butorphanol and apomorphine both increase sedation. Use Caution/Monitor.

            • cabergoline

              apomorphine and cabergoline both increase dopaminergic effects. Use Caution/Monitor.

            • captopril

              apomorphine, captopril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood pressure.

            • carbinoxamine

              carbinoxamine and apomorphine both increase sedation. Use Caution/Monitor.

            • carisoprodol

              carisoprodol and apomorphine both increase sedation. Use Caution/Monitor.

            • cenobamate

              cenobamate, apomorphine. Either increases effects of the other by sedation. Use Caution/Monitor.

            • chloral hydrate

              chloral hydrate and apomorphine both increase sedation. Use Caution/Monitor.

            • chlordiazepoxide

              chlordiazepoxide and apomorphine both increase sedation. Use Caution/Monitor.

            • chloroquine

              chloroquine increases toxicity of apomorphine by QTc interval. Use Caution/Monitor.

            • chlorpheniramine

              chlorpheniramine and apomorphine both increase sedation. Use Caution/Monitor.

            • chlorpromazine

              chlorpromazine and apomorphine both increase sedation. Use Caution/Monitor.

            • chlorzoxazone

              chlorzoxazone and apomorphine both increase sedation. Use Caution/Monitor.

            • citalopram

              apomorphine and citalopram both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • clemastine

              clemastine and apomorphine both increase sedation. Use Caution/Monitor.

            • clobazam

              apomorphine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

            • clomipramine

              clomipramine and apomorphine both increase sedation. Use Caution/Monitor.

            • clonazepam

              clonazepam and apomorphine both increase sedation. Use Caution/Monitor.

            • clorazepate

              clorazepate and apomorphine both increase sedation. Use Caution/Monitor.

            • clozapine

              clozapine and apomorphine both increase sedation. Use Caution/Monitor.

              apomorphine and clozapine both increase QTc interval. Use Caution/Monitor.

            • codeine

              codeine and apomorphine both increase sedation. Use Caution/Monitor.

            • crizotinib

              crizotinib and apomorphine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • cyclizine

              cyclizine and apomorphine both increase sedation. Use Caution/Monitor.

            • cyclobenzaprine

              cyclobenzaprine and apomorphine both increase sedation. Use Caution/Monitor.

            • cyproheptadine

              cyproheptadine and apomorphine both increase sedation. Use Caution/Monitor.

            • dantrolene

              dantrolene and apomorphine both increase sedation. Use Caution/Monitor.

            • daridorexant

              apomorphine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

            • dasatinib

              apomorphine and dasatinib both increase QTc interval. Use Caution/Monitor.

            • degarelix

              apomorphine and degarelix both increase QTc interval. Use Caution/Monitor.

            • desflurane

              desflurane and apomorphine both increase sedation. Use Caution/Monitor.

            • desipramine

              desipramine and apomorphine both increase sedation. Use Caution/Monitor.

              apomorphine and desipramine both increase QTc interval. Use Caution/Monitor.

            • deutetrabenazine

              apomorphine and deutetrabenazine both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).

            • dexchlorpheniramine

              dexchlorpheniramine and apomorphine both increase sedation. Use Caution/Monitor.

            • dexmedetomidine

              dexmedetomidine and apomorphine both increase sedation. Use Caution/Monitor.

            • diazepam

              diazepam and apomorphine both increase sedation. Use Caution/Monitor.

            • difelikefalin

              difelikefalin and apomorphine both increase sedation. Use Caution/Monitor.

            • difenoxin hcl

              difenoxin hcl and apomorphine both increase sedation. Use Caution/Monitor.

            • dimenhydrinate

              dimenhydrinate and apomorphine both increase sedation. Use Caution/Monitor.

            • diphenhydramine

              diphenhydramine and apomorphine both increase sedation. Use Caution/Monitor.

            • diphenoxylate hcl

              diphenoxylate hcl and apomorphine both increase sedation. Use Caution/Monitor.

            • donepezil

              donepezil and apomorphine both increase QTc interval. Use Caution/Monitor.

            • doxepin

              doxepin and apomorphine both increase sedation. Use Caution/Monitor.

              doxepin and apomorphine both increase QTc interval. Use Caution/Monitor.

            • doxylamine

              doxylamine and apomorphine both increase sedation. Use Caution/Monitor.

            • droperidol

              droperidol and apomorphine both increase sedation. Use Caution/Monitor.

            • efavirenz

              efavirenz and apomorphine both increase QTc interval. Use Caution/Monitor.

            • eliglustat

              apomorphine and eliglustat both increase QTc interval. Use Caution/Monitor.

              eliglustat and apomorphine both increase QTc interval. Use Caution/Monitor.

            • erythromycin base

              apomorphine and erythromycin base both increase QTc interval. Use Caution/Monitor.

            • erythromycin ethylsuccinate

              apomorphine and erythromycin ethylsuccinate both increase QTc interval. Use Caution/Monitor.

            • erythromycin lactobionate

              apomorphine and erythromycin lactobionate both increase QTc interval. Use Caution/Monitor.

            • erythromycin stearate

              apomorphine and erythromycin stearate both increase QTc interval. Use Caution/Monitor.

            • escitalopram

              escitalopram increases toxicity of apomorphine by QTc interval. Use Caution/Monitor.

            • estazolam

              estazolam and apomorphine both increase sedation. Use Caution/Monitor.

            • ethanol

              apomorphine and ethanol both increase sedation. Use Caution/Monitor.

            • etomidate

              etomidate and apomorphine both increase sedation. Use Caution/Monitor.

            • ezogabine

              ezogabine, apomorphine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.

            • fingolimod

              fingolimod and apomorphine both increase QTc interval. Use Caution/Monitor.

            • fluconazole

              apomorphine and fluconazole both increase QTc interval. Use Caution/Monitor.

            • fluoxetine

              apomorphine and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely.

            • fluphenazine

              fluphenazine and apomorphine both increase sedation. Use Caution/Monitor.

            • flurazepam

              flurazepam and apomorphine both increase sedation. Use Caution/Monitor.

            • formoterol

              apomorphine and formoterol both increase QTc interval. Use Caution/Monitor.

            • fostemsavir

              apomorphine and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

            • gemifloxacin

              apomorphine and gemifloxacin both increase QTc interval. Use Caution/Monitor.

            • gemtuzumab

              apomorphine and gemtuzumab both increase QTc interval. Use Caution/Monitor.

            • gilteritinib

              apomorphine and gilteritinib both increase QTc interval. Use Caution/Monitor.

            • goserelin

              goserelin increases toxicity of apomorphine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

            • haloperidol

              haloperidol and apomorphine both increase sedation. Use Caution/Monitor.

              haloperidol and apomorphine both increase QTc interval. Use Caution/Monitor.

            • histrelin

              histrelin increases toxicity of apomorphine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

            • hydromorphone

              hydromorphone and apomorphine both increase sedation. Use Caution/Monitor.

            • hydroxyzine

              hydroxyzine and apomorphine both increase sedation. Use Caution/Monitor.

              apomorphine and hydroxyzine both increase QTc interval. Use Caution/Monitor.

            • iloperidone

              iloperidone and apomorphine both increase sedation. Use Caution/Monitor.

            • imipramine

              imipramine and apomorphine both increase sedation. Use Caution/Monitor.

            • indacaterol, inhaled

              indacaterol, inhaled, apomorphine. QTc interval. Use Caution/Monitor. Drugs that are known to prolong the QTc interval may have an increased the risk of ventricular arrhythmias.

            • indapamide

              apomorphine and indapamide both increase QTc interval. Use Caution/Monitor.

            • isradipine

              apomorphine and isradipine both increase QTc interval. Use Caution/Monitor.

            • itraconazole

              apomorphine and itraconazole both increase QTc interval. Use Caution/Monitor.

            • ketamine

              ketamine and apomorphine both increase sedation. Use Caution/Monitor.

            • ketoconazole

              ketoconazole and apomorphine both increase QTc interval. Use Caution/Monitor.

            • ketotifen, ophthalmic

              apomorphine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

            • lapatinib

              apomorphine and lapatinib both increase QTc interval. Use Caution/Monitor.

            • lenvatinib

              apomorphine and lenvatinib both increase QTc interval. Use Caution/Monitor. Lenvatinib prescribing information recommends monitoring ECG closely when coadministered with QT prolonging drugs.

            • leuprolide

              leuprolide increases toxicity of apomorphine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

            • levalbuterol

              apomorphine and levalbuterol both increase QTc interval. Use Caution/Monitor.

            • levodopa

              apomorphine and levodopa both increase dopaminergic effects. Use Caution/Monitor. Combination may enhance efficacy. Monitor for hypotension.

            • levoketoconazole

              levoketoconazole and apomorphine both increase QTc interval. Use Caution/Monitor.

            • levorphanol

              levorphanol and apomorphine both increase sedation. Use Caution/Monitor.

            • lithium

              apomorphine and lithium both increase QTc interval. Use Caution/Monitor.

            • loperamide

              apomorphine and loperamide both increase QTc interval. Use Caution/Monitor.

            • lorazepam

              lorazepam and apomorphine both increase sedation. Use Caution/Monitor.

            • loxapine

              loxapine and apomorphine both increase sedation. Use Caution/Monitor.

            • loxapine inhaled

              loxapine inhaled and apomorphine both increase sedation. Use Caution/Monitor.

            • lurasidone

              lurasidone decreases effects of apomorphine by pharmacodynamic antagonism. Use Caution/Monitor. Antipsychotics may diminish the therapeutic effect of anti-parkinson's agents.

            • maprotiline

              maprotiline and apomorphine both increase sedation. Use Caution/Monitor.

            • maraviroc

              maraviroc, apomorphine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

            • marijuana

              apomorphine and marijuana both increase sedation. Use Caution/Monitor.

            • melatonin

              apomorphine and melatonin both increase sedation. Use Caution/Monitor.

            • meperidine

              meperidine and apomorphine both increase sedation. Use Caution/Monitor.

            • meprobamate

              apomorphine and meprobamate both increase sedation. Use Caution/Monitor.

            • metaxalone

              metaxalone and apomorphine both increase sedation. Use Caution/Monitor.

            • methadone

              methadone and apomorphine both increase sedation. Use Caution/Monitor.

            • methocarbamol

              methocarbamol and apomorphine both increase sedation. Use Caution/Monitor.

            • methyldopa

              apomorphine and methyldopa both increase dopaminergic effects. Use Caution/Monitor.

            • methylphenidate

              apomorphine, methylphenidate. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Potential for additive CNS stimulation.

            • metoclopramide

              metoclopramide decreases levels of apomorphine by pharmacodynamic antagonism. Use Caution/Monitor. Avoid combination if possible.

            • midazolam

              midazolam and apomorphine both increase sedation. Use Caution/Monitor.

            • midazolam intranasal

              midazolam intranasal, apomorphine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

            • mifepristone

              mifepristone, apomorphine. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.

            • mirtazapine

              apomorphine and mirtazapine both increase sedation. Use Caution/Monitor.

            • morphine

              morphine and apomorphine both increase sedation. Use Caution/Monitor.

            • motherwort

              apomorphine and motherwort both increase sedation. Use Caution/Monitor.

            • nabilone

              apomorphine and nabilone both increase sedation. Use Caution/Monitor.

            • nalbuphine

              nalbuphine and apomorphine both increase sedation. Use Caution/Monitor.

            • nortriptyline

              nortriptyline and apomorphine both increase sedation. Use Caution/Monitor.

              apomorphine and nortriptyline both increase QTc interval. Use Caution/Monitor.

            • olanzapine

              olanzapine and apomorphine both increase sedation. Use Caution/Monitor.

            • olodaterol inhaled

              apomorphine and olodaterol inhaled both increase QTc interval. Use Caution/Monitor. Drugs that prolong the QTc interval and may potentiate the effects of beta2 agonists on the cardiovascular system; increased risk of ventricular arrhythmias

            • opium tincture

              opium tincture and apomorphine both increase sedation. Use Caution/Monitor.

            • orphenadrine

              orphenadrine and apomorphine both increase sedation. Use Caution/Monitor.

            • osilodrostat

              osilodrostat and apomorphine both increase QTc interval. Use Caution/Monitor.

            • osimertinib

              osimertinib and apomorphine both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval.

            • oxazepam

              oxazepam and apomorphine both increase sedation. Use Caution/Monitor.

            • oxycodone

              oxycodone and apomorphine both increase sedation. Use Caution/Monitor.

            • oxymorphone

              oxymorphone and apomorphine both increase sedation. Use Caution/Monitor.

            • ozanimod

              ozanimod and apomorphine both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.

            • paliperidone

              paliperidone and apomorphine both increase sedation. Use Caution/Monitor.

            • papaverine

              apomorphine and papaverine both increase sedation. Use Caution/Monitor.

            • pasireotide

              apomorphine and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.

            • pentazocine

              pentazocine and apomorphine both increase sedation. Use Caution/Monitor.

            • pentobarbital

              pentobarbital and apomorphine both increase sedation. Use Caution/Monitor.

            • perphenazine

              perphenazine and apomorphine both increase sedation. Use Caution/Monitor.

            • phenobarbital

              phenobarbital and apomorphine both increase sedation. Use Caution/Monitor.

            • phenylephrine PO

              apomorphine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

            • pramipexole

              apomorphine and pramipexole both increase dopaminergic effects. Use Caution/Monitor.

            • primaquine

              apomorphine and primaquine both increase QTc interval. Use Caution/Monitor.

            • primidone

              primidone and apomorphine both increase sedation. Use Caution/Monitor.

            • prochlorperazine

              prochlorperazine and apomorphine both increase sedation. Use Caution/Monitor.

            • promethazine

              promethazine and apomorphine both increase sedation. Use Caution/Monitor.

            • propofol

              propofol and apomorphine both increase sedation. Use Caution/Monitor.

              apomorphine and propofol both increase QTc interval. Use Caution/Monitor.

            • protriptyline

              protriptyline and apomorphine both increase sedation. Use Caution/Monitor.

            • quazepam

              quazepam and apomorphine both increase sedation. Use Caution/Monitor.

            • quetiapine

              quetiapine and apomorphine both increase sedation. Use Caution/Monitor.

              quetiapine, apomorphine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Avoid use with drugs that prolong QT and in patients with risk factors for prolonged QT interval. Postmarketing cases show QT prolongation with overdose in patients with concomitant illness or with drugs known to cause electrolyte imbalance or prolong QT.

            • quinine

              apomorphine and quinine both increase QTc interval. Use Caution/Monitor.

            • ramelteon

              apomorphine and ramelteon both increase sedation. Use Caution/Monitor.

            • ranolazine

              apomorphine and ranolazine both increase QTc interval. Use Caution/Monitor.

            • rilpivirine

              rilpivirine increases toxicity of apomorphine by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • risperidone

              risperidone and apomorphine both increase sedation. Use Caution/Monitor.

              apomorphine and risperidone both increase QTc interval. Use Caution/Monitor.

            • romidepsin

              apomorphine and romidepsin both increase QTc interval. Use Caution/Monitor.

            • ropinirole

              apomorphine and ropinirole both increase dopaminergic effects. Use Caution/Monitor.

            • scullcap

              apomorphine and scullcap both increase sedation. Use Caution/Monitor.

            • secobarbital

              secobarbital and apomorphine both increase sedation. Use Caution/Monitor.

            • selpercatinib

              selpercatinib increases toxicity of apomorphine by QTc interval. Use Caution/Monitor.

            • sertraline

              apomorphine and sertraline both increase QTc interval. Use Caution/Monitor.

            • sevoflurane

              sevoflurane and apomorphine both increase sedation. Use Caution/Monitor.

            • shepherd's purse

              apomorphine and shepherd's purse both increase sedation. Use Caution/Monitor.

            • solifenacin

              apomorphine and solifenacin both increase QTc interval. Use Caution/Monitor.

            • solriamfetol

              apomorphine and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

            • sorafenib

              sorafenib and apomorphine both increase QTc interval. Use Caution/Monitor.

            • stiripentol

              stiripentol, apomorphine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

            • sufentanil

              sufentanil and apomorphine both increase sedation. Use Caution/Monitor.

            • sunitinib

              apomorphine and sunitinib both increase QTc interval. Use Caution/Monitor.

            • tacrolimus

              apomorphine and tacrolimus both increase QTc interval. Use Caution/Monitor.

            • tapentadol

              tapentadol and apomorphine both increase sedation. Use Caution/Monitor.

            • telavancin

              apomorphine and telavancin both increase QTc interval. Use Caution/Monitor.

            • temazepam

              temazepam and apomorphine both increase sedation. Use Caution/Monitor.

            • thiothixene

              thiothixene and apomorphine both increase sedation. Use Caution/Monitor.

            • topiramate

              apomorphine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • tramadol

              tramadol and apomorphine both increase sedation. Use Caution/Monitor.

            • trazodone

              trazodone and apomorphine both increase sedation. Use Caution/Monitor.

            • triazolam

              triazolam and apomorphine both increase sedation. Use Caution/Monitor.

            • triclabendazole

              apomorphine and triclabendazole both increase QTc interval. Use Caution/Monitor.

            • trifluoperazine

              trifluoperazine and apomorphine both increase sedation. Use Caution/Monitor.

            • trimipramine

              trimipramine and apomorphine both increase sedation. Use Caution/Monitor.

              apomorphine and trimipramine both increase QTc interval. Use Caution/Monitor.

            • triptorelin

              triptorelin increases toxicity of apomorphine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.

            • valbenazine

              valbenazine and apomorphine both increase QTc interval. Use Caution/Monitor.

            • vardenafil

              apomorphine and vardenafil both increase QTc interval. Use Caution/Monitor.

            • voclosporin

              voclosporin, apomorphine. Either increases effects of the other by QTc interval. Use Caution/Monitor.

            • voriconazole

              apomorphine and voriconazole both increase QTc interval. Use Caution/Monitor.

            • vorinostat

              apomorphine and vorinostat both increase QTc interval. Use Caution/Monitor.

            • ziconotide

              apomorphine and ziconotide both increase sedation. Use Caution/Monitor.

            Minor (9)

            • acetazolamide

              acetazolamide will increase the level or effect of apomorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • anastrozole

              anastrozole will increase the level or effect of apomorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • cyclophosphamide

              cyclophosphamide will increase the level or effect of apomorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • eucalyptus

              apomorphine and eucalyptus both increase sedation. Minor/Significance Unknown.

            • flecainide

              apomorphine and flecainide both increase QTc interval. Minor/Significance Unknown.

            • larotrectinib

              larotrectinib will increase the level or effect of apomorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ruxolitinib topical

              apomorphine will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sage

              apomorphine and sage both increase sedation. Minor/Significance Unknown.

            • trimethobenzamide

              trimethobenzamide decreases effects of apomorphine by pharmacodynamic antagonism. Minor/Significance Unknown. Trimethobenzamide may decrease the emetic response to apomorphine; monitor for additive CNS effects.

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            Adverse Effects

            >10%

            SC

            • Yawning (40%)
            • Dyskinesia (35%)
            • Drowsiness or somnolence (35%)
            • Nausea or vomiting (30%)
            • Injection site reaction (26%)
            • Dizziness or postural hypotension (20%)
            • Rhinorrhea (20%)
            • Bruising (16%)
            • Chest pain/pressure/angina (15%)

            SL

            • Nausea (21-28%)
            • Oral/pharyngeal soft tissue swelling (1-15%)
            • Somnolence (11-13%)
            • Oral/pharyngeal soft tissue pain and paresthesia (2-13%)
            • Dizziness (9-11%)

            1-10%

            SC

            • Hallucination or confusion (10%)
            • Edema/swelling of extremities (10%)
            • Granuloma (4%)
            • Pruritus (2%)

            SL

            • Headache (6-8%)
            • Rhinorrhea (6-7%)
            • Oral mucosal erythema (4-7%)
            • Vomiting (4-7%)
            • Fatigue (3-7%)
            • Oral ulceration and stomatitis (2-7%)
            • Hypersensitivity (6%)
            • Fall (4-6%)
            • Hyperhidrosis (4-6%)
            • Dry mouth (1-6%)
            • Laceration (1-6%)
            • Syncope/hypotension (2-4%)

            Postmarketing Reports

            Hemolytic anemia

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            Warnings

            Contraindications

            Hypersensitivity, including angioedema or anaphylaxis

            Sulfite/sulfur allergies (Apokyn contains sodium metabisulfite)

            Do not use 5-HT3 antagonists, including antiemetics (eg, granisetron, dolasetron, ondansetron, palonosetron) - risk of profound hypotension and loss of consciousness

            Cautions

            Subcutaneous use only; thrombus formation and pulmonary embolism have followed IV administration owing to crystallization of apomorphine

            Severe nausea and vomiting occurs at recommended doses; because of this, pretreat or treat with trimethobenzamide; trimethobenzamide reduces incidence of nausea and vomiting during first 4 weeks of therapy; patients treated with trimethobenzamide experience greater incidence of somnolence, dizziness and falls; benefit of treatment with trimethobenzamide must be balanced with risk for those adverse events, and treatment with trimethobenzamide should only be continued as long as necessary to control nausea and vomiting, which should generally be no longer than 2 months

            Closely monitor patients with mild and moderate hepatic impairment

            Falling asleep during activities of daily living and daytime somnolence may occur

            Oral mucosal irritaiton reported with SL product

            Syncope and hypotension/orthostatic hypotension may occur

            Falls may occur, or increase owing to underlying postural instability, possible autonomic instability, and syncope caused by low blood pressure

            May cause hallucinations and psychotic-like behavior

            May cause dyskinesia or exacerbate pre-existing dyskinesia (reported with SC administration)

            May cause problems with impulse control and impulsive behaviors; consider dose reduction or discontinuing

            Coronary events (eg, angina, MI, cardiac arrest, and/or sudden death) reported in clinical trials; apomorphine reduces resting systolic and diastolic BP and may have the potential to exacerbate ischemia

            Dose-related QT prolongation observed with therapeutic doses of SC apomorphine; although the extent of systemic exposure and peak plasma concentration of apomorphine are lower following the maximum recommended SL dose (30 mg) than following the maximum recommended dose of SC apomorphine (6 mg), QTc prolongation cannot be excluded with SL administration

            Withdrawal-emergent hyperpyrexia and confusion reported

            Cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, and cardiac valvulopathy have been reported in some patients treated with ergot-derived dopaminergic agents; these complications are thought to be associated with ergoline structure dopamine agonists, whether other nonergot derived dopamine agonists (eg, apomorphine) can cause these reactions is unknown

            Hypersensitivity/allergic reactions characterized by urticaria, rash, pruritus, and/or various manifestations of angioedema may occur with SL or SC dosing; SC has sulfite excipient; sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people

            Rare incidences of priapism reported during clinical trials

            Retinal atrophy detected at all SC doses in albino rat; retinal atrophy/degeneration has been observed in albino rats treated with other dopamine agonists for prolonged periods (~2 years)

            Hemolytic anemia

            • Hemolytic anemia requiring hospitalization reported in the postmarketing setting; many of reported cases included positive direct antiglobulin test (Coombs test), suggesting a potential immune-mediated hemolysis
            • Severe anemia, angina, and dyspnea have occurred with hemolytic anemia; some patients were treated with high dose glucocorticoids or blood transfusions
            • Hemolytic anemia can appear at any time after apomorphine treatment; if a patient develops anemia while receiving therapy, consider a workup for hemolytic anemia; if hemolytic anemia occurs, consider discontinuing treatment

            Drug interaction oveview

            • 5HT3 Antagonists
              • Contraindicated with 5HT3 antagonists (eg, ondansetron, granisetron, dolasetron, palonosetron)
              • Profound hypotension and loss of consciousness observed when SC apomorphine was administered with ondansetron
            • Antihypertensives and vasodilators
              • Coadministration may decrease blood pressure
              • In a study of SC apomorphine coadministered with SL nitroglycerin, a greater decrease in blood pressure was observed than apomorphine alone
              • Advise patients to lie down before and after taking SL nitroglycerin
            • Alcohol
              • Avoid drinking alcohol after taking apomorphine
              • Coadministration may decrease blood pressure
            • Dopamine antagonists
              • Dopamine antagonists such as neuroleptics (eg, phenothiazine, butyrophenones, thioxantenes) or metoclopramide may diminish the effect of apomorphine (a dopamine agonist)
            • QT prolonging drugs
              • Caution of coadministered with other drugs that prolong QT interval

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            Pregnancy & Lactation

            Pregnancy

            Adequate data on the developmental risk associated with use of apomorphine are not available in pregnant women

            In animal reproduction studies, apomorphine had adverse developmental effects in rats (increased neonatal deaths) and rabbits (increased incidence of malformation) when administered during pregnancy at clinically relevant doses; these doses were also associated with maternal toxicity

            Lactation

            Unknown if distributed in human breast milk

            Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Morphine derivative; nonergoline dopamine agonist of D2-type receptors within the caudate putamen in the brain

            Absorption

            Peak plasma time

            • SC: 10-60 min
            • SL: 30-60 min

            Distribution

            Vd

            • SC: 218 L
            • SL: 3630 L

            Metabolism

            Route of metabolism is unknown; potential metabolic routes include sulfation, oxidation, glucuronidation, and N-demethylation

            Elimination

            Half-life

            • SC: 40 min
            • SL: 1.7 hr

            Clearance

            • SC: 223 L/hr
            • SL: 1440 L/hr

            Excretion

            • SC: Urine (93%); feces (16%)
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            Administration

            Initial dose and dose titrations should be performed by a healthcare provider

            Measure blood pressure and pulse in supine and standing positions before and after dosing

            SL Administration

            Must be administered whole, do not cut, chew or swallow

            Before each dose, drink water to moisten mouth to help film dissolve more easily

            Film disintegrates in ~3 minutes

            Dose titration

            • Dose initiation should occur when patient is in an “off” state and in setting where clinician can monitor blood pressure and pulse
            • Instruct patients to not take their regular morning dose of carbidopa/levodopa or any other adjunctive Parkinson disease medications, and to take their last dose of carbidopa/levodopa (or adjunctive medications) no later than midnight the night before
            • If patient tolerates 10-mg dose and responds adequately, the starting dose should be 10 mg, used prn, up to 5 times per day, to treat “off” episodes
            • Insufficient response
              • If 10-mg dose tolerated, but response is insufficient, resume patient’s usual Parkinson disease medications and up-titration with apomorphine generally within 3 days
              • Increase dosage by 5-mg increments and assess response
              • Continue titration in a similar manner, under physician supervision, until effective and tolerable dose achieved

            SC Administration

            For subcutaneous (SC) administration only; thrombus formation and pumonary embolism have followed IV administration owing to crystallization of apomorphine

            Test dose

            • Begin dosing when patients are in an “off” state
            • Initial dose should be a 2 mg test dose in a setting where medical personnel can closely monitor blood pressure and pulse; both supine and standing blood pressure and pulse should be checked predose and at 20 minutes, 40 minutes, and 60 minutes postdose (and after 60 minutes, if there is significant hypotension at 60 minutes)
            • Patients who develop clinically significant orthostatic hypotension in response to this test dose should not be considered candidates for treatment
            • If the patient tolerates the 2-mg dose, and responds adequately, the starting dose should be 2 mg, used on an as needed basis to treat recurring “off” episodes
            • If needed, the dose can be increased in 1-mg increments every few days on an outpatient basis
            • Patient tolerates 2-mg test dose but does not respond
              • 4 mg may be administered under medical supervision, at least 2 hr after initial test dose, at the next observed “off” period
              • If 4-mg test dose tolerated and patient responded, the initial maintenance dose should be 3 mg used on an as needed basis to treat recurring “off” episodes as an outpatient
              • If needed, the dose can be increased in 1-mg increments every few days on an outpatient basis
            • Patient does not tolerate 4-mg test dose
              • If 4-mg test dose not tolerated, a 3-mg test dose may be administered during a separate “off” period under medical supervision (ie, at least 2 hr after the previous dose)
              • If 3-mg test dose tolerated, the initial maintenance dose should be 2 mg used on an as needed basis to treat existing “off” episodes
              • If needed, and the 2-mg dose is tolerated, the dose can be increased to 3 mg after a few days
              • In such a patient, the dose should ordinarily not be increased to 4 mg on an outpatient basis

            Retreatment and dose interruption

            • If a single dose is ineffective for a particular “off” period, a second dose should not be given for that “off” episode
            • The efficacy of the safety of administering a second dose for a single “off” episode has not been studied systematically
            • Do not administer a repeat dose sooner than 2 hr after the last dose
            • Patients who have an interruption in therapy >1 week should be restarted on a 2-mg dose and gradually titrated to effect and tolerability

            Storage

            SC injection: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)

            SL film: Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F); keep in foil pouch until ready to administer

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Kynmobi sublingual
            -
            10 mg film
            Kynmobi sublingual
            -
            10 mg film

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            apomorphine subcutaneous

            APOMORPHINE - INJECTION

            (A-poe-MOR-feen)

            COMMON BRAND NAME(S): Apokyn

            USES: This medication is used to treat the symptoms of Parkinson's disease. It can improve your ability to move during frequent "off" periods. It can decrease shakiness (tremor), stiffness, slowed movement, and unsteadiness. This medication is thought to work by helping to restore the balance of a certain natural substance (dopamine) in the brain.Apomorphine is used to treat "off" episodes when they occur. It is not used to prevent "off" episodes. This drug should not be used instead of your usual medications for Parkinson's disease. Continue taking all your medications as directed by your doctor.

            HOW TO USE: Read the Patient Information Leaflet and Instructions for Use if available from your pharmacist before you start using apomorphine and each time you get a refill. If you have any questions, consult your doctor or pharmacist.Learn all preparation and usage instructions in the product package. If any of the information is unclear, consult your doctor or pharmacist.Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Check the dose carefully before injecting. Apomorphine is given by the milliliter, not by the milligram. There are 10 milligrams of drug in each milliliter of this liquid, so if the wrong measuring unit is used, you may accidentally inject 10 times the amount of drug you need. Be sure you have the correct dose to prevent accidental overdose. If you are not sure how to measure your dose correctly, consult your pharmacist before injecting.If you are using the prefilled cartridge/pen, keep track of the doses used to make sure there is enough medication left in the device to give you a full dose.Clean the injection site before injecting. Inject this medication under the skin as needed to treat decreased/frozen muscle movement ("off" episode) as directed by your doctor. You may need to use this medication several times a day. Do not use a second injection for the same "off" episode. Wait at least 2 hours between injections.Do not inject this medication into a vein. It is important to change the location of the injection site with each dose to avoid problem areas under the skin. Choose a different injection site with each dose. The abdomen, thighs, and upper arms are recommended sites for the injection. Do not inject into skin that is irritated, sore, or infected. Learn how to store and discard needles and medical supplies safely. Never reuse syringes or needles. Consult your pharmacist for details.Dosage is based on your medical condition and response to treatment. To decrease the risk of side effects (such as nausea, drowsiness, low blood pressure) when you first start using apomorphine, your doctor will slowly increase your dosage until the best dose for you is reached. Your doctor will usually have you use the first dose in the office where your blood pressure can be checked and you can be watched for side effects. A health care professional will also teach you to inject this medication correctly. Nausea is very common with this medication. To decrease the risk of nausea, your doctor may direct you to start taking another medication (such as trimethobenzamide) 3 days before your first dose of apomorphine and to continue taking as directed for up to 2 months.Use this medication as prescribed. If you stop using this medication for longer than 1 week, you may need to increase your dose slowly back to your previous dosage. Talk with your doctor about how to restart the medication. Do not stop using this medication without your doctor's approval.If you are using this medication frequently and suddenly stop using it, you may have withdrawal symptoms (such as anxiety, depression, confusion, fever, muscle stiffness). To help prevent withdrawal, your doctor may lower your dose slowly. Withdrawal is more likely if you have used apomorphine for a long time or in high doses. Tell your doctor or pharmacist right away if you have withdrawal.Rarely, abnormal drug-seeking behavior (drug abuse) is possible with this medication. Do not increase your dose or use it more frequently than prescribed. Properly stop the medication when so directed.Tell your doctor if your condition lasts or gets worse.

            SIDE EFFECTS: Redness/swelling/pain/itching at the injection site, nausea, vomiting, headache, sweating, dizziness, drowsiness, yawning, or runny nose may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: uncontrolled movements, mental/mood changes (such as confusion, agitation, hallucinations), muscle cramps/spasm, swelling of the hands/legs/ankles/feet, unusual strong urges (such as increased gambling, increased sexual urges), unusual tiredness, pale skin.Get medical help right away if you have any very serious side effects, including: chest pain, shortness of breath, unusually fast/pounding/irregular heartbeat, severe dizziness, fainting, trouble speaking, vision changes, weakness on one side of the body.Some people using apomorphine have fallen asleep suddenly during their usual daily activities (such as talking on the phone, driving). In some cases, sleep occurred without any feelings of drowsiness beforehand. This sleep effect may occur anytime during treatment with apomorphine even if you have used this medication for a long time. If you experience increased sleepiness or fall asleep during the day, do not drive or take part in other possibly dangerous activities until you have discussed this effect with your doctor. Your risk of this sleep effect is increased by using alcohol or other medications that can make you drowsy. See also Precautions section.You may also develop a sudden drop in blood pressure that can cause dizziness, nausea, and fainting. This effect may also increase your risk of a fall. This drop in blood pressure is more likely when you are first starting the medication, when your dose is increased, or when you get up suddenly. To lower your risk, get up slowly from a sitting or lying position. Avoid alcohol.Rarely, males may have a painful or prolonged erection lasting 4 or more hours. If this occurs, stop using this drug and get medical help right away, or permanent problems could occur.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before using apomorphine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients (such as sulfites), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: asthma, heart problems (such as chest pain, heart attack), slow/fast/irregular heartbeat (such as arrhythmia), mental/mood disorders (such as confusion, hallucinations, psychosis, schizophrenia), kidney problems, liver problems, symptoms of low blood pressure (such as dizziness, fainting), sleep disorder (such as sleep apnea, narcolepsy), stroke or other brain problem.Apomorphine may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can rarely cause serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using apomorphine, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using apomorphine safely.This drug may make you dizzy or drowsy. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis). See also Side Effects section.Older adults may be at greater risk for the side effects of this drug, especially falls, hallucinations, and QT prolongation (see above).During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is unknown if this drug passes into breast milk. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: alosetron, antipsychotics (such as chlorpromazine, haloperidol, thiothixene), certain drugs for nausea (including metoclopramide, phenothiazines such as prochlorperazine, serotonin blockers such as ondansetron, granisetron), drugs for high blood pressure (including beta blockers such as atenolol), vasodilators (such as nitrates), "water pills" (diuretics such as furosemide, thiazides).Many drugs besides apomorphine may affect the heart rhythm (QT prolongation), including amiodarone, dofetilide, pimozide, procainamide, quinidine, sotalol, macrolide antibiotics (such as erythromycin), among others.Tell your doctor or pharmacist if you are taking other products that cause drowsiness including alcohol, marijuana (cannabis), antihistamines (such as cetirizine, diphenhydramine), drugs for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants (such as carisoprodol, cyclobenzaprine), and opioid pain relievers (such as codeine, hydrocodone).Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: very severe nausea/vomiting, loss of consciousness.

            NOTES: Do not share this medication with others.

            MISSED DOSE: Not applicable.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Syringes can be filled the night before use and stored in the refrigerator until the next day. Discard this type of pre-filled syringe if not used in 24 hours.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            Information last revised September 2022. Copyright(c) 2023 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.