apomorphine (Rx)

Brand and Other Names:Apokyn
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection solution

  • 10mg/mL (30mg/3mL pen injector)
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Parkinson Disease

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

Initial: 2 mg (0.2 mL) SC

Also see Administration for details regarding test dose

Dose titration

  • Titrate on the basis of effectiveness and tolerance, up to a maximum dose of 6 mg
  • 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

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
  • Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron, coadministration with 5HT3 antagonists (eg, ondansetron, granisetron, dolasetron, palonosetron) are contraindicated

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

Hepatic Impairment

Mild to moderate impairment: Use caution

Severe impairment: Safety and efficacy not established

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

Safety and efficacy not established

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Interactions

Interaction Checker

and apomorphine

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Dizziness or postural hypotension (20%)

            Dyskinesia (35%)

            Injection site reaction (26%)

            Nausea or vomiting (30%)

            Somnolence (35%)

            Yawning (40%)

            1-10%

            Anxiety

            Arthralgia

            Back pain

            CHF

            Confusion (10%)

            Depression

            Edema (10%)

            Hallucinations (10%)

            Headache

            Injection site pain

            Insomnia

            Limb pain

            Rhinorrhea (10%)

            UTI

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            Warnings

            Contraindications

            Hypersensitivity to apomorphine

            Sulfite/sulfur allergies (contains sulfite)

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

            Cautions

            For 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, premedicate with trimethobenzamide (see Dosing and Uses); 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 two months

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

            Syncope and hypotension/orthostatic hypotension may occur

            Falls may occur, or increase

            May cause hallucinations and psychotic-like behavior

            May cause dyskinesia or exacerbate pre-existing dyskinesia

            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

            May prolong QTc and cause torsades de pointes or sudden death

            Withdrawal-emergent hyperpyrexia and confusion reported

            Patients with Parkinson disease have a higher risk for melanoma compared with the general population; it is unclear if this is due to the disease or medications; providers are advised to monitor for melanoma regularly

            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

            Rare incidences of priapism reported during clinical trials

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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

            Pharmacokinetics

            Peak Plasma Time:10-60 min

            Half-life, elimination: 30-60 min

            Vd: 218 L

            Metabolism: Sulfation, oxidation, glucuronidation, N-demethylation, and cetechol-O methyltransferase

            Excretion: Urine (93%); feces (16%)

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            Administration

            SC Administration

            For subcutaneous administration only

            The initial dose and dose titrations should be performed by a healthcare provider

            Blood pressure and pulse should be measured in the supine and standing position before and after dosing

            Test dose

            • Begin dosing when patients are in an “off” state
            • The 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 the initial test dose, at the next observed “off” period
              • If the patient tolerates and responds to a test dose of 4 mg, 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 a 4 mg test dose is 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 the 3 mg test dose is 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

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

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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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