Apomorphine Hydrochloride

Name: Apomorphine Hydrochloride

Introduction

Nonergot-derivative dopamine receptor agonist.1 4

Uses for Apomorphine Hydrochloride

Hypomobility Episodes Associated with Parkinson’s Disease

Acute, intermittent treatment of episodes of hypomobility (i.e., “off” episodes, including end-of-dose “wearing off” and unpredictable “on-off” episodes) associated with advanced Parkinson’s disease (designated an orphan drug by FDA for this use).1 2 3 4 6 5 8 9 11 12 13 14

Used as an adjunct to other antiparkinsonian agents (e.g., levodopa, oral dopamine receptor agonists).1 2 5 8 11

Acute Poisoning

Formerly used to induce vomiting in the early management of acute oral drug overdose and in certain cases of oral poisoning (dose: 5–6 mg sub-Q)†.15

Apomorphine Hydrochloride Dosage and Administration

General

  • Administer an antiemetic (i.e., trimethobenzamide hydrochloride 300 mg orally 3 times daily) beginning 3 days prior to initiation of apomorphine; continue for the first 2 months of therapy or until tolerance to nausea and vomiting develops.1 11

  • Avoid certain other antiemetic agents (i.e., selective 5-HT3 receptor antagonists, dopamine-receptor antagonists [metoclopramide, phenothiazines]).1 4 (See Contraindications under Cautions and Specific Drugs under Interactions.)

Administration

Sub-Q Administration

Administer by sub-Q injection using the dosing pen on an as-needed basis to reverse “off” episodes.1

Administer sub-Q injections in the abdomen, thigh, or upper arm; rotate injection sites.1

Test dose: Administer all test doses in a medical setting where BP can be closely monitored.1 Measure supine and standing BP prior to and 20, 40, and 60 minutes after each test dose.1

Test dose: Determine dose when patient is experiencing an “off” episode.1 Induction of an “off” state can be facilitated by withholding the patient’s antiparkinsonian agents overnight.1

Do not administer IV; possibility of serious adverse effects (e.g., thrombosis, pulmonary embolism).1

Dosage

Available as apomorphine hydrochloride; dosage expressed in terms of the salt.1

Provide dosing instructions for the patient or their caregiver in mL; dose on the dosing pen device is expressed in terms of mL.1

Titrate dose according to patient’s response and tolerance.1

Adults

Hypomobility Episodes Associated with Parkinson’s Disease Sub–Q

Initial test dose is 0.2 mL (2 mg).1 If the 0.2-mL (2-mg) dose is effective and tolerated, this dose may be used on an as-needed, outpatient basis.1 If necessary, the dose may be increased in 0.1-mL (1-mg) increments every few days.1

Patient is not a candidate for apomorphine therapy if clinically significant orthostatic hypotension occurs in response to initial 0.2-mL (2-mg) test dose.1

For patients who tolerate, but do not respond to the initial 0.2-mL (2-mg) test dose, administer a second test dose of 0.4 mL (4 mg) at the next observed “off” period, no sooner than 2 hours after the initial test dose.1 If the 0.4-mL (4-mg) dose is effective and tolerated, a 0.3-mL (3-mg) dose may be used on an as-needed, outpatient basis.1 If necessary, the dose may be increased in 0.1-mL (1-mg) increments every few days.1

For patients who respond, but do not tolerate the 0.4-mL (4-mg) test dose, administer a third test dose of 0.3 mL (3 mg) at the next observed “off” period, but no sooner than 2 hours after the 0.4-mL (4-mg) test dose.1 If the 0.3-mL (3-mg) dose is effective and tolerated, a 0.2-mL (2-mg) dose may be used on an as-needed, outpatient basis.1 If the 0.2-mL (2-mg) dose is tolerated, the dose may be increased, if needed, to 0.3 mL (3 mg) after a few days.1 The dose should not usually be increased to 0.4 mL (4 mg) on an outpatient basis in these patients.1

In clinical studies, most patients responded to doses of 0.3–0.6 mL (3–6 mg); average frequency of dosing was 3 times daily.1

If therapy has been interrupted for >1 week, reinitiate at a dose of 0.2 mL (2 mg) and gradually titrate to effect.1

Prescribing Limits

Adults

Hypomobility Episodes Associated with Parkinson’s Disease Sub-Q

No more than one dose of apomorphine should be administered for treatment of a single “off” episode.1 Safety and efficacy of a second dose during the same hypomobility episode in patients not responding to the initial dose have not been established.1

Doses >0.6 mL (6 mg) not associated with additional therapeutic effect and are not recommended.1

Limited experience with >5 doses per day or daily dosages >2 mL (20 mg).1

Special Populations

Hepatic Impairment

No special recommendations for patients with hepatic impairment.1 (See Hepatic Impairment under Cautions.)

Renal Impairment

In patients with mild or moderate renal impairment, initial test dose and subsequent starting dose is 0.1 mg (1 mg).1

Apomorphine Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Bioavailability following sub-Q administration is 100%.1 Peak plasma concentrations achieved in 10–60 minutes.1

Onset

Following sub-Q administration, therapeutic response usually achieved in 10–20 minutes.1 2 5 8 12

Duration

Approximately 60 minutes.1 2 5 8 12

Special Populations

In individuals with moderate hepatic impairment receiving a single sub-Q dose of apomorphine, peak plasma concentrations and AUC were increased 25 and 10%, respectively, compared with healthy individuals.1

In patients with moderate renal impairment receiving a single sub-Q dose of apomorphine, peak plasma concentrations and AUC were increased 50 and 16%, respectively, compared with healthy individuals.1 Time to peak plasma concentrations was not affected by renal status.1

Distribution

Extent

Maximum cerebrospinal fluid concentrations are <10% of peak plasma concentrations.1

Elimination

Metabolism

Routes of metabolism not known.1 Potential metabolic routes include sulfation, N–demethylation, glucuronidation, and oxidation.1

Half-life

40 minutes.1

Special Populations

Half-life not affected by renal status.1

Stability

Storage

Parenteral

Injection

25°C (may be exposed to 15–30°C).1

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