Apokyn

apomorphine hydrochloride

APO-go (UK), Apokyn

Pharmacologic class: Dopaminergic, dopamine-receptor agonist

Therapeutic class: Antiparkinsonian

Pregnancy risk category C

Action

Unclear. May stimulate postsynaptic dopamine D₂-type receptors in caudate-putamen of brain.

Availability

Ampules: 10 mg/ml in 2- and 3-ml cartridges

Indications and dosages

➣ Acute intermittent treatment of hypomobility and "off" ("end-of-dose wearing off" and unpredictable "on/off") episodes associated with Parkinson's disease

Adults: 0.2-ml (2-mg) test dose injected subcutaneously during "off" state in setting where medical personnel can monitor blood pressure. If patient tolerates test dose, give 0.2 ml subcutaneously p.r.n. to treat "off" episodes no sooner than 2 hours after previous dose. Establish dosage based on tolerance and efficacy; increase in 0.1-ml (1 mg) increments, usually to 0.3 to 0.4 ml. Maximum dosage, 0.6 ml up to five times daily.

Patient who tolerates but doesn't respond to test dose may receive 0.4 ml (4 mg) at next observed "off" period, but no sooner than 2 hours after initial 0.2-ml test dose. If patient tolerates 0.4-ml test dose, give starting dosage of 0.3 ml (3 mg) p.r.n. to treat "off" episodes. If needed, increase in increments of 0.1 ml every few days on outpatient basis.

If patient doesn't tolerate 0.4-ml test dose, 0.3-ml test dose may be given during separate "off" period no sooner than 2 hours after 0.4-ml test dose.

If patient tolerates 0.3-ml test dose, starting dosage should be 0.2 ml p.r.n. to treat existing "off" episodes. If needed and if patient tolerates 0.2-ml dose, dosage can be increased to 0.3 ml after several days; in this case, it ordinarily shouldn't be increased to 0.4 ml on outpatient basis.

Dosage adjustment

• Mild or moderate renal impairment

Contraindications

• Hypersensitivity to drug or its components

• Concurrent use of 5-hydroxytryptamine₃ (5-HT₃) antagonists (such as alosetron, dolasetron, granisetron, ondansetron, palonosetron)

Precautions

Use cautiously in:

• renal or hepatic impairment

• pregnant or breastfeeding patients

• children (safety and efficacy not established).

Administration

• If prescribed, give trimethobenzamide (antiemetic) for 3 days before starting apomorphine and continuing throughout therapy.

• Give only by subcutaneous injection.

See Don't give I.V. because this may cause serious adverse events, such as I.V. crystallization of apomorphine, leading to thrombus formation and pulmonary embolism.

• Titrate dosage based on efficacy and patient tolerance.

• Check supine and standing blood pressure before giving test dose and 20, 40, and 60 minutes after. If patient experiences clinically significant orthostatic hypotension in response to test dose, don't give drug.

Adverse reactions

CNS: drowsiness, somnolence, dizziness, hallucinations, confusion, syncope, dyskinesias

CV: orthostatic hypotension, chest pain, chest pressure, angina, cardiac valvulopathy

EENT: rhinorrhea

GI: nausea, vomiting, retroperitoneal fibrosis

GU: priapism

Respiratory: pulmonary infiltrates, pleural effusion, pleural thickening

Other: yawning, edema of extremities, injection site reactions, abuse potential, allergic reactions

Interactions

Drug-drug. Antihypertensive agents, vasodilators: increased incidence of hypotension, myocardial infarction, serious pneumonia, serious falls, bone and joint injuries

Dopamine antagonists: decreased apomorphine efficacy

5-HT₃ antagonists: profound hypotension

Drug-behaviors. Alcohol use: additive drowsiness and somnolence

Patient monitoring

• Monitor for serious cardiovascular and respiratory adverse reactions.

• Monitor for unexpected somnolence, which may interfere with daily activities.

Patient teaching

• Instruct patient to take drug as described in patient instruction leaflet.

• Make sure patient knows that dosages are in milliliters, not milligrams.

• Instruct patient to rotate injection site.

• Inform patient that drug may cause hallucinations and unexpected sleepiness.

• Tell patient that drug may cause blood pressure to drop. Caution him to rise slowly from sitting or lying position.

• Urge patient to consult prescriber before taking other drugs.

• Caution patient not to use alcohol during therapy.

• Advise patient to avoid driving and other hazardous activities until drug effects are known.

• As appropriate, review all other significant adverse reactions and interactions, especially those related to the drugs mentioned above.

apomorphine

(a-po-mor-feen) apomorphine,

Apokyn

(trade name)

Classification

Therapeutic: antiparkinson agents
Pharmacologic: dopamine agonists
Pregnancy Category: C

Indications

Acute, intermittent treatment of hypomotility, “off” episodes due to advanced Parkinson's disease.

Action

Stimulation of specific dopamine receptors improves motor function.

Therapeutic effects

Improved motor function.

Pharmacokinetics

Absorption: Well absorbed (100%) following subcut administration.Distribution: Enters CSF.Metabolism and Excretion: Unknown.Half-life: 40 min.

Time/action profile (blood levels)

ROUTE	ONSET	PEAK	DURATION
subcut	rapid	10–60 min	2 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity to apomorphine or bisulfites; Concurrent use of 5HT₃ antagonists (granisetron, ondansetron, palonosetron, alosetron, dolasetron); Major psychotic disorder (may exacerbate condition); Lactation: May appear in human milk; discontinue medication or discontinue breast-feeding.Use Cautiously in: Hypokalemia, hypomagnesemia, bradycardia, congenital QTc prolongation or concurrent use of drugs causing QTc prolongation (↑ risk of serious arrhythmias); Mild to moderate renal impairment (↓ starting dose); Mild to moderate hepatic impairment; Obstetric: Use only if clearly needed; Pediatric: Safety not established; Geriatric: ↑ risk of confusion/hallucinations, falls, and cardiac, respiratory, and gastrointestinal events.Exercise Extreme Caution in: Cardiovascular or cerebrovascular disease (may exacerbate condition).

Adverse Reactions/Side Effects

Central nervous system

dizziness (most frequent)
hallucinations (most frequent)
somnolence (most frequent)
aggressive behavior
agitation
confusion
delirium
delusions
disorientation
drowsiness
headache
paranoid ideation
urges (gambling, sexual)

Ear, Eye, Nose, Throat

rhinorrhea (most frequent)

Cardiovascular

cardiac arrest (life-threatening)
chest pain (most frequent)
hypotension (most frequent)
angina
HF
QTc prolongation

Gastrointestinal

nausea (most frequent)
vomiting (most frequent)

Genitourinary

priapism

Dermatologic

flushing (most frequent)
pallor (most frequent)
sweating (most frequent)
melanoma

Local

injection site pain

Musculoskeletal

arthralgia
back pain
limb pain

Neurologic

aggravation of Parkinson's disease
dyskinesia

Miscellaneous

yawning (most frequent)

Interactions

Drug-Drug interaction

Profound hypotension, loss of consciousness occurs with 5-HT₃ antagonists.↑ risk of hypotension with alcohol, antihypertensives, vasodilators, especially nitrates.Dopamine antagonists, including neuroleptics and metoclopramide may ↓ efficacy.Drugs that prolong the QT interval may ↑ risk of QT interval prolongation.

Route/Dosage

Subcutaneous (Adults) Test dose—0.2 mL (2 mg); with further assessment and monitoring, doses should be titrated at 0.1 mL (1 mg) less than highest tolerated dose. Doses may be ↑ by 0.1 mL (1 mg) every few days as an outpatient or no more frequently than every 2 hours in a supervised setting. Only single doses should be used during a particular off period. If more than one week passes between doses, titration should be restarted at the 0.2 mL (2 mg) level. Doses should not exceed 0.6 mL (6 mg).

Availability

Solution for injection (contains bisulfites): 10 mg/mL

Nursing implications

Nursing assessment

Assess for nausea and vomiting; severe with recommended doses. Premedicate with an antiemetic prior to and for at least the first 2 mo of therapy. Do not administer 5-HT₃ antagonist; results in profound hypotension and loss of consciousness.
Monitor BP standing and lying during dose titration. Orthostatic hypotension may occur any time during therapy but occurs more frequently during initial therapy or with a dose increase.

Potential Nursing Diagnoses

Risk for injury (Adverse Reactions)

Implementation

Always prime the APOKYN pen before every injection and after loading a new cartridge.
- Never dial the dose or attempt to correct a dialing error with the BD pen needle in the skin, as this may result in an incorrect dose.
- Do not store or carry APOKYN pen with a pen needle attached. Use a new sterile BD pen needle with each injection.
Subcutaneous: Administer subcutaneously into stomach, upper arm, or upper leg. Pinch skin with finger and thumb and insert needle all the way into pinched skin. Push the injection button until a clicking sound is heard, and hold button for 5 min and gently rub injection site. Rotate site with each injection. Do not inject into skin that is red, sore, infected, or damaged. Solution should be clear and colorless; do not administer solution that is cloudy, green, or contains particles. Do not administer IV.
- Store apomorphine at room temperature. Syringes can be filled from ampules the night before and stored in the refrigerator until next day.

Patient/Family Teaching

Provide patient and caregiver with detailed instructions on preparation and injection of dose, use of dosing pen, storage, and disposal of equipment. Advise patient to read the Patient Package Insert and Directions for Use. Medication is dosed in mL, not mg. A dose of 1 mg is represented on dosing pen as 0.1 mL (1.0 mL equals 10 mg). Caution patient that apomorphine is not used to prevent “off” episodes and does not take the place of other medications for Parkinson's disease.
Advise patient to change positions slowly to prevent orthostatic hypotension. Caution patient to avoid drinking alcohol; will increase hypotensive effects of apomorphine.
May cause sudden bouts of falling asleep during activities of daily living. Advise patient to notify health care professional if daytime sleepiness occurs and to avoid other medications that cause drowsiness. May require discontinuation of apomorphine. Caution patients to avoid alcohol and other medications that cause sedation and to avoid driving and other activities requiring alertness until response to medication is known.
Caution patients that psychotic-like behavior including hallucinations (seeing or hearing things that are not real), confusion, excessive suspicion, aggressive behavior, agitation, delusional beliefs (believing things that are not real), and disorganized thinking may occur or worsen. Notify health care professional if this occurs.
Advise patient to notify health care professional if or new or increased gambling, sexual, or other intense urges occur.
Advise patient to have periodic skin exams to check for lesions that may be melanoma.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Advise patients to notify health care professional if pregnancy is planned or suspected or if breast feeding.

Evaluation/Desired Outcomes

Improvement in ability to control movements when used during an “off” episode of Parkinson's disease. May improve ability to walk, talk, or move around.